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1. Comprehensive ECG reference intervals in C57BL/6N substrains provide a generalizable guide for cardiac electrophysiology studies in mice

Author

Oestereicher, Manuela A., Wotton, Janine M., Ayabe, Shinya, Bou About, Ghina, Cheng, Tsz Kwan, Choi, Jae-Hoon, Clary, Dave, Dew, Emily M., Elfertak, Lahcen, Guimond, Alain, Haseli Mashhadi, Hamed, Heaney, Jason D., Kelsey, Lois, Keskivali-Bond, Piia, Lopez Gomez, Federico, Marschall, Susan, McFarland, Michael, Meziane , Hamid, Munoz Fuentes, Violeta, Nam , Ki-Hoan, Nichtová, Zuzana, Pimm, Dale, Bower, Lynette, Prochazka, Jan, Rozman, Jan, Santos, Luis, Stewart, Michelle, Tanaka, Nobuhiko, Ward, Christopher S., Willett, Amelia M. E., Wilson, Robert, Braun, Robert E., Dickinson, Mary E., Flenniken, Ann M., Herault, Yann, Lloyd, K. C. Kent, Mallon, Ann-Marie, McKerlie, Colin, Murray, Stephen A., Nutter, Lauryl M. J., Sedlacek, Radislav, Seong, Je Kyung, Sorg, Tania, Tamura, Masaru, Wells, Sara, Schneltzer, Elida, Fuchs, Helmut, Gailus-Durner, Valerie, Hrabe de Angelis, Martin, White, Jacqueline K., and Spielmann, Nadine

Published
2023
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2. A resource of targeted mutant mouse lines for 5,061 genes

Author

Birling, Marie-Christine, Yoshiki, Atsushi, Adams, David J, Ayabe, Shinya, Beaudet, Arthur L, Bottomley, Joanna, Bradley, Allan, Brown, Steve DM, Bürger, Antje, Bushell, Wendy, Chiani, Francesco, Chin, Hsian-Jean Genie, Christou, Skevoulla, Codner, Gemma F, DeMayo, Francesco J, Dickinson, Mary E, Doe, Brendan, Donahue, Leah Rae, Fray, Martin D, Gambadoro, Alessia, Gao, Xiang, Gertsenstein, Marina, Gomez-Segura, Alba, Goodwin, Leslie O, Heaney, Jason D, Hérault, Yann, de Angelis, Martin Hrabe, Jiang, Si-Tse, Justice, Monica J, Kasparek, Petr, King, Ruairidh E, Kühn, Ralf, Lee, Ho, Lee, Young Jae, Liu, Zhiwei, Lloyd, KC Kent, Lorenzo, Isabel, Mallon, Ann-Marie, McKerlie, Colin, Meehan, Terrence F, Fuentes, Violeta Munoz, Newman, Stuart, Nutter, Lauryl MJ, Oh, Goo Taeg, Pavlovic, Guillaume, Ramirez-Solis, Ramiro, Rosen, Barry, Ryder, Edward J, Santos, Luis A, Schick, Joel, Seavitt, John R, Sedlacek, Radislav, Seisenberger, Claudia, Seong, Je Kyung, Skarnes, William C, Sorg, Tania, Steel, Karen P, Tamura, Masaru, Tocchini-Valentini, Glauco P, Wang, Chi-Kuang Leo, Wardle-Jones, Hannah, Wattenhofer-Donzé, Marie, Wells, Sara, Wiles, Michael V, Willis, Brandon J, Wood, Joshua A, Wurst, Wolfgang, Xu, Ying, Teboul, Lydia, and Murray, Stephen A

Subjects
Biological Sciences, Genetics, Animals, Gene Deletion, Genetic Association Studies, Genome, Genotype, Information Dissemination, International Cooperation, Internet, Mice, Mice, Knockout, Mouse Embryonic Stem Cells, Mutagenesis, Phenotype, International Mouse Phenotyping Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for over 5,000 genes, including 2,850 novel null, 2,987 novel conditional- ready, and 4,433 novel reporter alleles.

Published
2021

4. Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation

Author

Gurumurthy, Channabasavaiah B, O’Brien, Aidan R, Quadros, Rolen M, Adams, John, Alcaide, Pilar, Ayabe, Shinya, Ballard, Johnathan, Batra, Surinder K, Beauchamp, Marie-Claude, Becker, Kathleen A, Bernas, Guillaume, Brough, David, Carrillo-Salinas, Francisco, Chan, Wesley, Chen, Hanying, Dawson, Ruby, DeMambro, Victoria, D’Hont, Jinke, Dibb, Katharine M, Eudy, James D, Gan, Lin, Gao, Jing, Gonzales, Amy, Guntur, Anyonya R, Guo, Huiping, Harms, Donald W, Harrington, Anne, Hentges, Kathryn E, Humphreys, Neil, Imai, Shiho, Ishii, Hideshi, Iwama, Mizuho, Jonasch, Eric, Karolak, Michelle, Keavney, Bernard, Khin, Nay-Chi, Konno, Masamitsu, Kotani, Yuko, Kunihiro, Yayoi, Lakshmanan, Imayavaramban, Larochelle, Catherine, Lawrence, Catherine B, Li, Lin, Lindner, Volkhard, Liu, Xian-De, Lopez-Castejon, Gloria, Loudon, Andrew, Lowe, Jenna, Jerome-Majewska, Loydie A, Matsusaka, Taiji, Miura, Hiromi, Miyasaka, Yoshiki, Morpurgo, Benjamin, Motyl, Katherine, Nabeshima, Yo-ichi, Nakade, Koji, Nakashiba, Toshiaki, Nakashima, Kenichi, Obata, Yuichi, Ogiwara, Sanae, Ouellet, Mariette, Oxburgh, Leif, Piltz, Sandra, Pinz, Ilka, Ponnusamy, Moorthy P, Ray, David, Redder, Ronald J, Rosen, Clifford J, Ross, Nikki, Ruhe, Mark T, Ryzhova, Larisa, Salvador, Ane M, Alam, Sabrina Shameen, Sedlacek, Radislav, Sharma, Karan, Smith, Chad, Staes, Katrien, Starrs, Lora, Sugiyama, Fumihiro, Takahashi, Satoru, Tanaka, Tomohiro, Trafford, Andrew W, Uno, Yoshihiro, Vanhoutte, Leen, Vanrockeghem, Frederique, Willis, Brandon J, Wright, Christian S, Yamauchi, Yuko, Yi, Xin, Yoshimi, Kazuto, Zhang, Xuesong, Zhang, Yu, Ohtsuka, Masato, Das, Satyabrata, Garry, Daniel J, Hochepied, Tino, Thomas, Paul, Parker-Thornburg, Jan, Adamson, Antony D, and Yoshiki, Atsushi

Subjects
Biological Sciences, Genetics, Biotechnology, Prevention, Alleles, Animals, Blastocyst, CRISPR-Associated Protein 9, CRISPR-Cas Systems, Factor Analysis, Statistical, Female, Male, Methyl-CpG-Binding Protein 2, Mice, Knockout, Microinjections, Regression Analysis, Reproducibility of Results, CRISPR-Cas9, Mouse, Transgenesis, Homology-directed repair, Conditional knockout mouse, Floxed allele, Oligonucleotide, Long single-stranded DNA, Machine learning, Reproducibility, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundCRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides as donors (referred herein as "two-donor floxing" method).ResultsWe re-evaluate the two-donor method from a consortium of 20 laboratories across the world. The dataset constitutes 56 genetic loci, 17,887 zygotes, and 1718 live-born mice, of which only 15 (0.87%) mice contain cKO alleles. We subject the dataset to statistical analyses and a machine learning algorithm, which reveals that none of the factors analyzed was predictive for the success of this method. We test some of the newer methods that use one-donor DNA on 18 loci for which the two-donor approach failed to produce cKO alleles. We find that the one-donor methods are 10- to 20-fold more efficient than the two-donor approach.ConclusionWe propose that the two-donor method lacks efficiency because it relies on two simultaneous recombination events in cis, an outcome that is dwarfed by pervasive accompanying undesired editing events. The methods that use one-donor DNA are fairly efficient as they rely on only one recombination event, and the probability of correct insertion of the donor cassette without unanticipated mutational events is much higher. Therefore, one-donor methods offer higher efficiencies for the routine generation of cKO animal models.

Published
2019

6. High-throughput discovery of novel developmental phenotypes

Author

McKay, Matthew, Urban, Barbara, Lund, Caroline, Froeter, Erin, LaCasse, Taylor, Mehalow, Adrienne, Gordon, Emily, Donahue, Leah Rae, Taft, Robert, Kutney, Peter, Dion, Stephanie, Goodwin, Leslie, Kales, Susan, Urban, Rachel, Palmer, Kristina, Pertuy, Fabien, Bitz, Deborah, Weber, Bruno, Goetz-Reiner, Patrice, Jacobs, Hughes, Le Marchand, Elise, El Amri, Amal, El Fertak, Leila, Ennah, Hamid, Ali-Hadji, Dalila, Ayadi, Abdel, Wattenhofer-Donze, Marie, Jacquot, Sylvie, André, Philippe, Birling, Marie-Christine, Pavlovic, Guillaume, Sorg, Tania, Morse, Iva, Benso, Frank, Stewart, Michelle E, Copley, Carol, Harrison, Jackie, Joynson, Samantha, Guo, Ruolin, Qu, Dawei, Spring, Shoshana, Yu, Lisa, Ellegood, Jacob, Morikawa, Lily, Shang, Xueyuan, Feugas, Pat, Creighton, Amie, Castellanos Penton, Patricia, Danisment, Ozge, Griggs, Nicola, Tudor, Catherine L, Green, Angela L, Icoresi Mazzeo, Cecilia, Siragher, Emma, Lillistone, Charlotte, Tuck, Elizabeth, Gleeson, Diane, Sethi, Debarati, Bayzetinova, Tanya, Burvill, Jonathan, Habib, Bishoy, Weavers, Lauren, Maswood, Ryea, Miklejewska, Evelina, Woods, Michael, Grau, Evelyn, Newman, Stuart, Sinclair, Caroline, Brown, Ellen, Ayabe, Shinya, Iwama, Mizuho, and Murakami, Ayumi

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Biotechnology, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Animals, Conserved Sequence, Disease, Embryo, Mammalian, Genes, Essential, Genes, Lethal, Genome-Wide Association Study, High-Throughput Screening Assays, Humans, Imaging, Three-Dimensional, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Penetrance, Phenotype, Polymorphism, Single Nucleotide, Sequence Homology, International Mouse Phenotyping Consortium, Jackson Laboratory, Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris, Charles River Laboratories, MRC Harwell, Toronto Centre for Phenogenomics, Wellcome Trust Sanger Institute, RIKEN BioResource Center, General Science & Technology
Abstract

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.

Published
2016

7. Response to correspondence on “Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation”

Author

Gurumurthy, Channabasavaiah B., O’Brien, Aidan R., Quadros, Rolen M., Adams, Jr, John, Alcaide, Pilar, Ayabe, Shinya, Ballard, Johnathan, Batra, Surinder K., Beauchamp, Marie-Claude, Becker, Kathleen A., Bernas, Guillaume, Brough, David, Carrillo-Salinas, Francisco, Chan, Wesley, Chen, Hanying, Dawson, Ruby, DeMambro, Victoria, D’Hont, Jinke, Dibb, Katharine, Eudy, James D., Gan, Lin, Gao, Jing, Gonzales, Amy, Guntur, Anyonya, Guo, Huiping, Harms, Donald W., Harrington, Anne, Hentges, Kathryn E., Humphreys, Neil, Imai, Shiho, Ishii, Hideshi, Iwama, Mizuho, Jonasch, Eric, Karolak, Michelle, Keavney, Bernard, Khin, Nay-Chi, Konno, Masamitsu, Kotani, Yuko, Kunihiro, Yayoi, Lakshmanan, Imayavaramban, Larochelle, Catherine, Lawrence, Catherine B., Li, Lin, Lindner, Volkhard, Liu, Xian-De, Lopez-Castejon, Gloria, Loudon, Andrew, Lowe, Jenna, Jerome-Majeweska, Loydie, Matsusaka, Taiji, Miura, Hiromi, Miyasaka, Yoshiki, Morpurgo, Benjamin, Motyl, Katherine, Nabeshima, Yo-ichi, Nakade, Koji, Nakashiba, Toshiaki, Nakashima, Kenichi, Obata, Yuichi, Ogiwara, Sanae, Ouellet, Mariette, Oxburgh, Leif, Piltz, Sandra, Pinz, Ilka, Ponnusamy, Moorthy P., Ray, David, Redder, Ronald J., Rosen, Clifford J., Ross, Nikki, Ruhe, Mark T., Ryzhova, Larisa, Salvador, Ane M., Alam, Sabrina Shameen, Sedlacek, Radislav, Sharma, Karan, Smith, Chad, Staes, Katrien, Starrs, Lora, Sugiyama, Fumihiro, Takahashi, Satoru, Tanaka, Tomohiro, Trafford, Andrew, Uno, Yoshihiro, Vanhoutte, Leen, Vanrockeghem, Frederique, Willis, Brandon J., Wright, Christian S., Yamauchi, Yuko, Yi, Xin, Yoshimi, Kazuto, Zhang, Xuesong, Zhang, Yu, Ohtsuka, Masato, Das, Satyabrata, Garry, Daniel J., Hochepied, Tino, Thomas, Paul, Parker-Thornburg, Jan, Adamson, Antony D., Yoshiki, Atsushi, Schmouth, Jean-Francois, Golovko, Andrei, Thompson, William R., Lloyd, K. C. Kent, Wood, Joshua A., Cowan, Mitra, Mashimo, Tomoji, Mizuno, Seiya, Zhu, Hao, Kasparek, Petr, Liaw, Lucy, Miano, Joseph M., and Burgio, Gaetan

Published
2021
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10. Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes

Author

Matsumura, Kensuke, Seiriki, Kaoru, Okada, Shota, Nagase, Masashi, Ayabe, Shinya, Yamada, Ikuko, Furuse, Tamio, Shibuya, Hirotoshi, Yasuda, Yuka, Yamamori, Hidenaga, Fujimoto, Michiko, Nagayasu, Kazuki, Yamamoto, Kana, Kitagawa, Kohei, Miura, Hiroki, Gotoda-Nishimura, Nanaka, Igarashi, Hisato, Hayashida, Misuzu, Baba, Masayuki, Kondo, Momoka, Hasebe, Shigeru, Ueshima, Kosei, Kasai, Atsushi, Ago, Yukio, Hayata-Takano, Atsuko, Shintani, Norihito, Iguchi, Tokuichi, Sato, Makoto, Yamaguchi, Shun, Tamura, Masaru, Wakana, Shigeharu, Yoshiki, Atsushi, Watabe, Ayako M., Okano, Hideyuki, Takuma, Kazuhiro, Hashimoto, Ryota, Hashimoto, Hitoshi, and Nakazawa, Takanobu

Published
2020
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14. DAJIN enables multiplex genotyping to simultaneously validate intended and unintended target genome editing outcomes

Author

Kuno, Akihiro, primary, Ikeda, Yoshihisa, additional, Ayabe, Shinya, additional, Kato, Kanako, additional, Sakamoto, Kotaro, additional, Suzuki, Sayaka R., additional, Morimoto, Kento, additional, Wakimoto, Arata, additional, Mikami, Natsuki, additional, Ishida, Miyuki, additional, Iki, Natsumi, additional, Hamada, Yuko, additional, Takemura, Megumi, additional, Daitoku, Yoko, additional, Tanimoto, Yoko, additional, Dinh, Tra Thi Huong, additional, Murata, Kazuya, additional, Hamada, Michito, additional, Muratani, Masafumi, additional, Yoshiki, Atsushi, additional, Sugiyama, Fumihiro, additional, Takahashi, Satoru, additional, and Mizuno, Seiya, additional

Published
2022
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15. Establishment of mouse line showing inducible priapism‐like phenotypes

Author

Hashimoto, Daiki, primary, Fujimoto, Kota, additional, Morioka, Shin, additional, Ayabe, Shinya, additional, Kataoka, Tomoya, additional, Fukumura, Ryutaro, additional, Ueda, Yuko, additional, Kajimoto, Mizuki, additional, Hyuga, Taiju, additional, Suzuki, Kentaro, additional, Hara, Isao, additional, Asamura, Shinichi, additional, Wakana, Shigeharu, additional, Yoshiki, Atsushi, additional, Gondo, Yoichi, additional, Tamura, Masaru, additional, Sasaki, Takehiko, additional, and Yamada, Gen, additional

Published
2022
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16. Author Reply to Peer Reviews of Multiplex genotyping method to validate the multiallelic genome editing outcomes using machine learning-assisted long-read sequencing

Author

Mizuno, Seiya, primary, Takahashi, Satoru, additional, Sugiyama, Fumihiro, additional, Yoshiki, Atsushi, additional, Muratani, Masafumi, additional, Hamada, Michito, additional, Murata, Kazuya, additional, Huong Dinh, Tra Thi, additional, Tanimoto, Yoko, additional, Daitoku, Yoko, additional, Takemura, Megumi, additional, Hamada, Yuko, additional, Iki, Natsumi, additional, Ishida, Miyuki, additional, Mikami, Natsuki, additional, Wakimoto, Arata, additional, Morimoto, Kento, additional, Suzuki, Sayaka, additional, Sakamoto, Kotaro, additional, Kato, Kanako, additional, Ayabe, Shinya, additional, Ikeda, Yoshihisa, additional, and Kuno, Akihiro, additional

Published
2021
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17. Mouse resources at the RIKEN BioResource Research Center and the National BioResource Project core facility in Japan

Author

Mizuno-Iijima, Saori, primary, Nakashiba, Toshiaki, additional, Ayabe, Shinya, additional, Nakata, Hatsumi, additional, Ike, Fumio, additional, Hiraiwa, Noriko, additional, Mochida, Keiji, additional, Ogura, Atsuo, additional, Masuya, Hiroshi, additional, Kawamoto, Shoko, additional, Tamura, Masaru, additional, Obata, Yuichi, additional, Shiroishi, Toshihiko, additional, and Yoshiki, Atsushi, additional

Published
2021
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18. Efficient production of large deletion and gene fragment knock-in mice mediated by genome editing with Cas9-mouse Cdt1 in mouse zygotes

Author

Mizuno-Iijima, Saori, primary, Ayabe, Shinya, additional, Kato, Kanako, additional, Matoba, Shogo, additional, Ikeda, Yoshihisa, additional, Dinh, Tra Thi Huong, additional, Le, Hoai Thu, additional, Suzuki, Hayate, additional, Nakashima, Kenichi, additional, Hasegawa, Yoshikazu, additional, Hamada, Yuko, additional, Tanimoto, Yoko, additional, Daitoku, Yoko, additional, Iki, Natsumi, additional, Ishida, Miyuki, additional, Ibrahim, Elzeftawy Abdelaziz Elsayed, additional, Nakashiba, Toshiaki, additional, Hamada, Michito, additional, Murata, Kazuya, additional, Miwa, Yoshihiro, additional, Okada-Iwabu, Miki, additional, Iwabu, Masato, additional, Yagami, Ken-ichi, additional, Ogura, Atsuo, additional, Obata, Yuichi, additional, Takahashi, Satoru, additional, Mizuno, Seiya, additional, Yoshiki, Atsushi, additional, and Sugiyama, Fumihiro, additional

Published
2021
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20. Multiplex genotyping method to validate the multiallelic genome editing outcomes using machine learning-assisted long-read sequencing

Author

Kuno, Akihiro, primary, Ikeda, Yoshihisa, additional, Ayabe, Shinya, additional, Kato, Kanako, additional, Sakamoto, Kotaro, additional, Suzuki, Sayaka, additional, Morimoto, Kento, additional, Wakimoto, Arata, additional, Mikami, Natsuki, additional, Ishida, Miyuki, additional, Iki, Natsumi, additional, Hamada, Yuko, additional, Takemura, Megumi, additional, Daitoku, Yoko, additional, Tanimoto, Yoko, additional, Huong Dinh, Tra Thi, additional, Murata, Kazuya, additional, Hamada, Michito, additional, Muratani, Masafumi, additional, Yoshiki, Atsushi, additional, Sugiyama, Fumihiro, additional, Takahashi, Satoru, additional, and Mizuno, Seiya, additional

Published
2020
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21. Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma

Author

Miura, Keiko, primary, Akashi, Takumi, additional, Namiki, Takeshi, additional, Hishima, Tsunekazu, additional, Bae, Yuan, additional, Sakurai, Urara, additional, Murano, Keimei, additional, Shiraishi, Junichi, additional, Warabi, Masahiro, additional, Tanizawa, Toru, additional, Tanaka, Michio, additional, Bhunchet, Ekapot, additional, Kumagai, Jiro, additional, Ayabe, Shinya, additional, Sekiya, Takahiro, additional, Ando, Noboru, additional, Shintaku, Hiroshi, additional, Kinowaki, Yuko, additional, Tomii, Shohei, additional, Kirimura, Susumu, additional, Kayamori, Kou, additional, Yamamoto, Kurara, additional, Ito, Takashi, additional, and Eishi, Yoshinobu, additional

Published
2020
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22. Generation ofB6‐Ddx4em1(CreERT2)Utr, a novelCreERT2knock‐in line, for germ cell lineage byCRISPR/Cas9

Author

Le, Hoai Thu, primary, Hasegawa, Yoshikazu, additional, Daitoku, Yoko, additional, Kato, Kanako, additional, Miznuo‐Iijima, Saori, additional, Dinh, Tra Thi Huong, additional, Kuba, Yumeno, additional, Osawa, Yuki, additional, Mikami, Natsuki, additional, Morimoto, Kento, additional, Ayabe, Shinya, additional, Tanimoto, Yoko, additional, Murata, Kazuya, additional, Yagami, Ken‐ichi, additional, Takahashi, Satoru, additional, Mizuno, Seiya, additional, and Sugiyama, Fumihiro, additional

Published
2020
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24. High-throughput discovery of novel developmental phenotypes

Author

Dickinson, Mary E., Flenniken, Ann M., Ji, Xiao, Teboul, Lydia, Wong, Michael D., White, Jacqueline K., Meehan, Terrence F., Weninger, Wolfgang J., Westerberg, Henrik, Adissu, Hibret, Baker, Candice N., Bower, Lynette, Brown, James M., Caddle, L. Brianna, Chiani, Francesco, Clary, Dave, Cleak, James, Daly, Mark J., Denegre, James M., Doe, Brendan, Dolan, Mary E., Edie, Sarah M., Fuchs, Helmut, Gailus-Durner, Valerie, Galli, Antonella, Gambadoro, Alessia, Gallegos, Juan, Guo, Shiying, Horner, Neil R., Hsu, Chih-Wei, Johnson, Sara J., Kalaga, Sowmya, Keith, Lance C., Lanoue, Louise, Lawson, Thomas N., Lek, Monkol, Mark, Manuel, Marschall, Susan, Mason, Jeremy, McElwee, Melissa L., Newbigging, Susan, Nutter, Lauryl M. J., Peterson, Kevin A., Ramirez-Solis, Ramiro, Rowland, Douglas J., Ryder, Edward, Samocha, Kaitlin E., Seavitt, John R., Selloum, Mohammed, Szoke-Kovacs, Zsombor, Tamura, Masaru, Trainor, Amanda G., Tudose, Ilinca, Wakana, Shigeharu, Warren, Jonathan, Wendling, Olivia, West, David B., Wong, Leeyean, Yoshiki, Atsushi, McKay, Matthew, Urban, Barbara, Lund, Caroline, Froeter, Erin, LaCasse, Taylor, Mehalow, Adrienne, Gordon, Emily, Donahue, Leah Rae, Taft, Robert, Kutney, Peter, Dion, Stephanie, Goodwin, Leslie, Kales, Susan, Urban, Rachel, Palmer, Kristina, Pertuy, Fabien, Bitz, Deborah, Weber, Bruno, Goetz-Reiner, Patrice, Jacobs, Hughes, Le Marchand, Elise, El Amri, Amal, El Fertak, Leila, Ennah, Hamid, Ali-Hadji, Dalila, Ayadi, Abdel, Wattenhofer-Donze, Marie, Jacquot, Sylvie, Andr, Philippe, Birling, Marie-Christine, Pavlovic, Guillaume, Sorg, Tania, Morse, Iva, Benso, Frank, Stewart, Michelle E., Copley, Carol, Harrison, Jackie, Joynson, Samantha, Guo, Ruolin, Qu, Dawei, Spring, Shoshana, Yu, Lisa, Ellegood, Jacob, Morikawa, Lily, Shang, Xueyuan, Feugas, Pat, Creighton, Amie, Castellanos Penton, Patricia, Danisment, Ozge, Griggs, Nicola, Tudor, Catherine L., Green, Angela L., Icoresi Mazzeo, Cecilia, Siragher, Emma, Lillistone, Charlotte, Tuck, Elizabeth, Gleeson, Diane, Sethi, Debarati, Bayzetinova, Tanya, Burvill, Jonathan, Habib, Bishoy, Weavers, Lauren, Maswood, Ryea, Miklejewska, Evelina, Woods, Michael, Grau, Evelyn, Newman, Stuart, Sinclair, Caroline, Brown, Ellen, Ayabe, Shinya, Iwama, Mizuho, Murakami, Ayumi, MacArthur, Daniel G., Tocchini-Valentini, Glauco P., Gao, Xiang, Flicek, Paul, Bradley, Allan, Skarnes, William C., Justice, Monica J., Parkinson, Helen E., Moore, Mark, Wells, Sara, Braun, Robert E., Svenson, Karen L., de Angelis, Martin Hrabe, Herault, Yann, Mohun, Tim, Mallon, Ann-Marie, Henkelman, R. Mark, Brown, Steve D. M., Adams, David J., Lloyd, K. C. Kent, McKerlie, Colin, Beaudet, Arthur L., Buan, Maja, and Murray, Stephen A.

Subjects
Phenotypes -- Research, Genetic research, High-throughput screening (Biochemical assaying) -- Methods, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts., Author(s): Mary E. Dickinson [1]; Ann M. Flenniken [2, 3]; Xiao Ji [4]; Lydia Teboul [5]; Michael D. Wong [2, 6]; Jacqueline K. White [7]; Terrence F. Meehan [8]; Wolfgang [...]

Published
2016
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25. Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: A multi-center evaluation

Author

Gurumurthy, Channabasavaiah B., O'Brien, Aidan, Quadros, Rolen M., Adams Jr, John, Alcaide, Pilar, Ayabe, Shinya, Ballard, John, Batra, Surinder K., Beauchamp, Marie-Claude, Becker, Kathleen A., Bernas, Guillaume, Jing, Gao, Khin, Nay Chi, Lowe, Jenna, Ross, Nikki, Starrs, Lora, Burgio, Gaetan, Gurumurthy, Channabasavaiah B., O'Brien, Aidan, Quadros, Rolen M., Adams Jr, John, Alcaide, Pilar, Ayabe, Shinya, Ballard, John, Batra, Surinder K., Beauchamp, Marie-Claude, Becker, Kathleen A., Bernas, Guillaume, Jing, Gao, Khin, Nay Chi, Lowe, Jenna, Ross, Nikki, Starrs, Lora, and Burgio, Gaetan

Abstract

Background CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides as donors (referred herein as “two-donor floxing” method). Results We re-evaluate the two-donor method from a consortium of 20 laboratories across the world. The dataset constitutes 56 genetic loci, 17,887 zygotes, and 1718 live-born mice, of which only 15 (0.87%) mice contain cKO alleles. We subject the dataset to statistical analyses and a machine learning algorithm, which reveals that none of the factors analyzed was predictive for the success of this method. We test some of the newer methods that use one-donor DNA on 18 loci for which the two-donor approach failed to produce cKO alleles. We find that the one-donor methods are 10- to 20-fold more efficient than the two-donor approach. Conclusion We propose that the two-donor method lacks efficiency because it relies on two simultaneous recombination events in cis, an outcome that is dwarfed by pervasive accompanying undesired editing events. The methods that use one-donor DNA are fairly efficient as they rely on only one recombination event, and the probability of correct insertion of the donor cassette without unanticipated mutational events is much higher. Therefore, one-donor methods offer higher efficiencies for the routine generation of cKO animal models.

Published
2019

26. Identification of genetic elements in metabolism by high-throughput mouse phenotyping

Author

Rozman, Jan, Rathkolb, Birgit, Meehan, Terrence F, Codner, Gemma F, Fiegel, Tanja, Ring, Natalie, Westerberg, Henrik, Greenaway, Simon, Sneddon, Duncan, Morgan, Hugh, Loeffler, Jorik, Stewart, Michelle E, Ramirez-Solis, Ramiro, Mason, Jeremy, Bradley, Allan, Skarnes, William C, Steel, Karen P, Maguire, Simon A, Dench, Joshua, Lafont, David, Vancollie, Valerie E, Pearson, Selina A, Gates, Amy S, Sanderson, Mark, Haselimashhadi, Hamed, Shannon, Carl, Anthony, Lauren F E, Sumowski, Maksymilian T, McLaren, Robbie S B, Doe, Brendan, Wardle-Jones, Hannah, Griffiths, Mark N D, Galli, Antonella, Swiatkowska, Agnieszka, Isherwood, Christopher M, Consortium, IMPC, Speak, Anneliese O, Cambridge, Emma L, Wilson, Heather M, Caetano, Susana S, Maguire, Anna Karin B, Adams, David J, Bottomley, Joanna, Ryder, Ed, Gleeson, Diane, Pouilly, Laurent, Hough, Tertius, Rousseau, Stephane, Auburtin, Aurélie, Reilly, Patrick, Ayadi, Abdel, Selloum, Mohammed, Wood, Joshua A, Clary, Dave, Havel, Peter, Tolentino, Todd, Tolentino, Heather, Mallon, Ann-Marie, Schuchbauer, Mike, Pedroia, Sheryl, Trainor, Amanda, Djan, Esi, Pham, Milton, Huynh, Alison, De Vera, Vincent, Seavitt, John, Gallegos, Juan, Garza, Arturo, Wells, Sara, Mangin, Elise, Senderstrom, Joel, Lazo, Iride, Mowrey, Kate, Bohat, Ritu, Samaco, Rodney, Veeraragavan, Surabi, Beeton, Christine, Kalaga, Sowmya, Kelsey, Lois, Santos, Luis, Vukobradovic, Igor, Berberovic, Zorana, Owen, Celeste, Qu, Dawei, Guo, Ruolin, Newbigging, Susan, Morikawa, Lily, Law, Napoleon, Shang, Xueyuan, Feugas, Patricia, Lelliott, Christopher J, Wang, Yanchun, Eskandarian, Mohammad, Zhu, Yingchun, Penton, Patricia, Laurin, Valerie, Clarke, Shannon, Lan, Qing, Sleep, Gillian, Creighton, Amie, Jacob, Elsa, White, Jacqueline K, Danisment, Ozge, Gertsenstein, Marina, Pereira, Monica, MacMaster, Suzanne, Tondat, Sandra, Carroll, Tracy, Cabezas, Jorge, Hunter, Jane, Clark, Greg, Bubshait, Mohammed, Oestereicher, Manuela A, Sorg, Tania, Miller, David, Sohel, Khondoker, Adissu, Hibret, Ganguly, Milan, Bezginov, Alexandr, Chiani, Francesco, Di Pietro, Chiara, Di Segni, Gianfranco, Ermakova, Olga, Ferrara, Filomena, Champy, Marie-France, Fruscoloni, Paolo, Gambadoro, Aalessia, Gastaldi, Serena, Golini, Elisabetta, La Sala, Gina, Mandillo, Silvia, Marazziti, Daniela, Massimi, Marzia, Matteoni, Rafaele, Orsini, Tiziana, Bower, Lynette R, Pasquini, Miriam, Raspa, Marcello, Rauch, Aline, Rossi, Gianfranco, Rossi, Nicoletta, Putti, Sabrina, Scavizzi, Ferdinando, Tocchini-Valentini, Giuseppe D, Wakana, Shigeharu, Suzuki, Tomohiro, Reynolds, Corey L, Tamura, Masaru, Kaneda, Hideki, Furuse, Tamio, Kobayashi, Kimio, Miura, Ikuo, Yamada, Ikuko, Obata, Yuichi, Yoshiki, Atsushi, Ayabe, Shinya, Chambers, J Nicole, Flenniken, Ann M, Chalupsky, Karel, Seisenberger, Claudia, Bürger, Antje, Beig, Joachim, Kühn, Ralf, Hörlein, Andreas, Schick, Joel, Oritz, Oskar, Giesert, Florian, Graw, Jochen, Murray, Stephen A, Ollert, Markus, Schmidt-Weber, Carsten, Stoeger, Tobias, Önder Yildirim, Ali, Eickelberg, Oliver, Klopstock, Thomas, Busch, Dirk H, Bekeredjian, Raffi, Zimmer, Andreas, Jacobsen, Jules O, Nutter, Lauryl M J, Smedley, Damian, Dickinson, Mary E, Benso, Frank, Morse, Iva, Kim, Hyoung-Chin, Lee, Ho, Cho, Soo Young, Svenson, Karen L, West, David, Tocchini-Valentini, Glauco P, Schütt, Christine, Beaudet, Arthur L, Bosch, Fatima, Braun, Robert B, Dobbie, Michael S, Gao, Xiang, Herault, Yann, Moshiri, Ala, Moore, Bret A, Kent Lloyd, K. C., McKerlie, Colin, Ravindranath, Aakash Chavan, Masuya, Hiroshi, Tanaka, Nobuhiko, Flicek, Paul, Parkinson, Helen E, Sedlacek, Radislav, Seong, Je Kyung, Wang, Chi-Kuang Leo, Moore, Mark, Brown, Steve D, Tschöp, Matthias H, Leuchtenberger, Stefanie, Wurst, Wolfgang, Klingenspor, Martin, Wolf, Eckhard, Beckers, Johannes, Machicao, Fausto, Peter, Andreas, Staiger, Harald, Häring, Hans-Ulrich, Grallert, Harald, Campillos, Monica, Sharma, Sapna, Maier, Holger, Fuchs, Helmut, Gailus-Durner, Valerie, Werner, Thomas, Hrabe de Angelis, Martin, Aguilar-Pimentel, Antonio, Becker, Lore, Treise, Irina, Moreth, Kristin, Garrett, Lillian, Kistler, Martin, Hölter, Sabine M, Zimprich, Annemarie, Marschall, Susan, Amarie, Oana V, Calzada-Wack, Julia, Neff, Frauke, Brachthäuser, Laura, Lengger, Christoph, Stoeger, Claudia, Zapf, Lilly, Willershäuser, Monja, Cho, Yi-Li, da Silva-Buttkus, Patricia, Kraiger, Markus J, Mayer-Kuckuk, Philipp, Gampe, Karen Kristine, Wu, Moya, Conte, Nathalie, Warren, Jonathan, Chen, Chao-Kung, Tudose, Ilinca, Brommage, Robert, Relac, Mike, Matthews, Peter, Cater, Heather L, Natukunda, Helen P, Cleak, James, Teboul, Lydia M, Clementson-Mobbs, Sharon, Szoke-Kovacs, Zsombor, Walling, Alison P, Johnson, Sara J, Rozman, Jan [0000-0002-8035-8904], Kistler, Martin [0000-0003-0116-7761], Mason, Jeremy [0000-0002-2796-5123], Lelliott, Christopher J [0000-0001-8087-4530], Herault, Yann [0000-0001-7049-6900], Kent Lloyd, KC [0000-0002-5318-4144], McKerlie, Colin [0000-0002-2232-0967], Flicek, Paul [0000-0002-3897-7955], Maier, Holger [0000-0003-2514-8290], Fuchs, Helmut [0000-0002-5143-2677], Hrabe de Angelis, Martin [0000-0002-7898-2353], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Blood Glucose, Candidate gene, Cancer Research, Basal Metabolism/genetics, Gene regulatory network, Obesity/genetics, genetics [Metabolic Diseases], General Physics and Astronomy, Genome-wide association study, Genome, Mice, genetics [Obesity], Triglycerides/metabolism, 2.1 Biological and endogenous factors, Gene Regulatory Networks, Aetiology, lcsh:Science, metabolism [Blood Glucose], Mice, Knockout, Multidisciplinary, genetics [Basal Metabolism], Phenotype, Area Under Curve, Diabetes Mellitus, Type 2/genetics, ddc:500, Technology Platforms, Type 2, metabolism [Triglycerides], Knockout, Science, Computational biology, Biology, genetics [Diabetes Mellitus, Type 2], General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Oxygen Consumption, Metabolic Diseases, Body Weight/genetics, Diabetes Mellitus, Genetics, Animals, Humans, Metabolic Diseases/genetics, Obesity, Gene, Gene knockout, Triglycerides, Oxygen Consumption/genetics, Blood Glucose/metabolism, genetics [Body Weight], Human Genome, Body Weight, Promoter, General Chemistry, genetics [Oxygen Consumption], High-Throughput Screening Assays, 030104 developmental biology, Diabetes Mellitus, Type 2, IMPC Consortium, lcsh:Q, Basal Metabolism, Genome-Wide Association Study
Abstract

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome., The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Published
2018

28. A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

Author

Bowl, Michael R., Simon, Michelle M., Ingham, Neil J., Greenaway, Simon, Santos, Luis, Cater, Heather, Taylor, Sarah, Mason, Jeremy, Kurbatova, Natalja, Pearson, Selina, Bower, Lynette R., Clary, Dave A., Meziane, Hamid, Reilly, Patrick, Minowa, Osamu, Kelsey, Lois, Allen, Sue, Clementson-Mobbs, Sharon, Codner, Gemma, Fray, Martin, Gardiner, Wendy, Joynson, Russell, Kenyon, Janet, Loeffler, Jorik, Nell, Barbara, Parker, Andrew, Quwailid, Deen, Stewart, Michelle, Walling, Alison, Zaman, Rumana, Chen, Chao Kung, Conte, Nathalie, Matthews, Peter, Relac, Mike, Tudose, Ilinca, Warren, Jonathan, Le Marchand, Elise, El Amri, Amal, El Fertak, Leila, Ennah, Hamid, Ali-Hadji, Dalila, Ayadi, Abdel, Wattenhofer-Donze, Marie, Moulaert, David, Jacquot, Sylvie, André, Philippe, Birling, Marie Christine, Pavlovic, Guillaume, Lalanne, Valérie, Lux, Aline, Riet, Fabrice, Mittelhaeuser, Christophe, Bour, Raphael, Guimond, Alain, Bam'Hamed, Chaouki, Leblanc, Sophie, Vasseur, Laurent, Selloum, Mohammed, Sorg, Tania, Ayabe, Shinya, Furuse, Tamio, Kaneda, Hideki, Kobayashi, Kimio, Masuya, Hiroshi, Miura, Ikuo, Obata, Yuichi, Suzuki, Tomohiro, Tamura, Masaru, Tanaka, Nobuhiko, Yamada, Ikuko, Yoshiki, Atsushi, Berberovic, Zorana, Bubshait, Mohammed, Cabezas, Jorge, Carroll, Tracy, Clark, Greg, Clarke, Shannon, Creighton, Amie, Danisment, Ozge, Eskandarian, Mohammad, Feugas, Patricia, Gertsenstein, Marina, Guo, Ruolin, Hunter, Jane, Jacob, Elsa, Lan, Qing, Laurin, Valerie, Law, Napoleon, MacMaster, Sue, Miller, David, Morikawa, Lily, Newbigging, Susan, Owen, Celeste, Penton, Patricia, Pereira, Monica, Qu, Dawei, Shang, Xueyuan, Sleep, Gillian, Sohel, Khondoker, Tondat, Sandra, Wang, Yanchun, Vukobradovic, Igor, Zhu, Yingchun, Chiani, Francesco, Di Pietro, Chiara, Di Segni, Gianfranco, Ermakova, Olga, Ferrara, Filomena, Fruscoloni, Paolo, Gambadoro, Aalessia, Gastaldi, Serena, Golini, Elisabetta, Sala, Gina La, Mandillo, Silvia, Marazziti, Daniela, Massimi, Marzia, Matteoni, Rafaele, Orsini, Tiziana, Pasquini, Miriam, Raspa, Marcello, Rauch, Aline, Rossi, Gianfranco, Rossi, Nicoletta, Putti, Sabrina, Scavizzi, Ferdinando, Tocchini-Valentini, Giuseppe D., Beig, Joachim, Bürger, Antje, Giesert, Florian, Graw, Jochen, Kühn, Ralf, Oritz, Oskar, Schick, Joel, Seisenberger, Claudia, Amarie, Oana, Garrett, Lillian, Hölter, Sabine M., Zimprich, Annemarie, Aguilar-Pimentel, Antonio, Beckers, Johannes, Brommage, Robert, Calzada-Wack, Julia, Fuchs, Helmut, Gailus-Durner, Valérie, Lengger, Christoph, Leuchtenberger, Stefanie, Maier, Holger, Marschall, Susan, Moreth, Kristin, Neff, Frauke, Östereicher, Manuela A., Rozman, Jan, Steinkamp, Ralph, Stoeger, Claudia, Treise, Irina, Stoeger, Tobias, Yildrim, Ali Önder, Eickelberg, Oliver, Becker, Lore, Klopstock, Thomas, Ollert, Markus, Busch, Dirk H., Schmidt-Weber, Carsten, Bekeredjian, Raffi, Zimmer, Andreas, Rathkolb, Birgit, Wolf, Eckhard, Klingenspor, Martin, Tocchini-Valentini, Glauco P., Gao, Xiang, Bradley, Allan, Skarnes, William C., Moore, Mark, Beaudet, Arthur L., Justice, Monica J., Seavitt, John, Dickinson, Mary E., Wurst, Wolfgang, De Angelis, Martin Hrabe, Herault, Yann, Wakana, Shigeharu, Nutter, Lauryl M.J., Flenniken, Ann M., McKerlie, Colin, Murray, Stephen A., Svenson, Karen L., Braun, Robert E., West, David B., Lloyd, K. C.Kent, Adams, David J., White, Jacqui, Karp, Natasha, Flicek, Paul, Smedley, Damian, Meehan, Terrence F., Parkinson, Helen E., Teboul, Lydia M., Wells, Sara, Steel, Karen P., Mallon, Ann Marie, Brown, Steve D.M., Mason, Jeremy [0000-0002-2796-5123], de Angelis, Martin Hrabe [0000-0002-7898-2353], Herault, Yann [0000-0001-7049-6900], Wakana, Shigeharu [0000-0001-8532-0924], McKerlie, Colin [0000-0002-2232-0967], Lloyd, KC Kent [0000-0002-5318-4144], Flicek, Paul [0000-0002-3897-7955], Smedley, Damian [0000-0002-5836-9850], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Cancer Research, Candidate gene, General Physics and Astronomy, Datasets as Topic, Mice, 2.1 Biological and endogenous factors, Protein Interaction Maps, Aetiology, lcsh:Science, Pediatric, Genetics, Mice, Knockout, Multidisciplinary, medicine.diagnostic_test, Hearing Tests, Ear, Phenotype, medicine.anatomical_structure, Technology Platforms, International Mouse Phenotyping Consortium, medicine.symptom, Biotechnology, Hearing Loss/epidemiology, Hearing loss, Knockout, 1.1 Normal biological development and functioning, Science, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Clinical Research, Underpinning research, medicine, otorhinolaryngologic diseases, Auditory system, Animals, Genetic Testing, IMPC, mouse, auditory dysfunction, Set (psychology), Hearing Loss, Gene, Genetic testing, Auditory dysfunction, Human Genome, General Chemistry, 030104 developmental biology, Protein Interaction Maps/genetics, lcsh:Q
Abstract

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function., The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

Published
2017

30. Re-Evaluating One-step Generation of Mice Carrying Conditional Alleles by CRISPR-Cas9-Mediated Genome Editing Technology

Author

Gurumurthy, Channabasavaiah, primary, Quadros, Rolen, additional, Adams, John, additional, Alcaide, Pilar, additional, Ayabe, Shinya, additional, Ballard, Johnathan, additional, Batra, Surinder K., additional, Beauchamp, Marie-Claude, additional, Becker, Kathleen A, additional, Bernas, Guillaume, additional, Brough, David, additional, Carrillo-Salinas, Francisco, additional, Dawson, Ruby, additional, DeMambro, Victoria, additional, D’Hont, Jinke, additional, Dibb, Katharine, additional, Eudy, James D., additional, Gan, Lin, additional, Gao, Jing, additional, Gonzales, Amy, additional, Guntur, Anyonya, additional, Guo, Huiping, additional, Harms, Donald W., additional, Harrington, Anne, additional, Hentges, Kathryn E., additional, Humphreys, Neil, additional, Imai, Shiho, additional, Ishii, Hideshi, additional, Iwama, Mizuho, additional, Jonasch, Eric, additional, Karolak, Michelle, additional, Keavney, Bernard, additional, Khin, Nay-Chi, additional, Konno, Masamitsu, additional, Kotani, Yuko, additional, Kunihiro, Yayoi, additional, Lakshmanan, Imayavaramban, additional, Larochelle, Catherine, additional, Lawrence, Catherine B., additional, Li, Lin, additional, Lindner, Volkhard, additional, Liu, Xian-De, additional, Lopez-Castejon, Gloria, additional, Loudon, Andrew, additional, Lowe, Jenna, additional, Jerome-Majeweska, Loydie, additional, Matsusaka, Taiji, additional, Miura, Hiromi, additional, Miyasaka, Yoshiki, additional, Morpurgo, Benjamin, additional, Motyl, Katherine, additional, Nabeshima, Yo-ichi, additional, Nakade, Koji, additional, Nakashiba, Toshiaki, additional, Nakashima, Kenichi, additional, Obata, Yuichi, additional, Ogiwara, Sanae, additional, Ouellet, Mariette, additional, Oxburgh, Leif, additional, Piltz, Sandra, additional, Pinz, Ilka, additional, Ponnusamy, Moorthy P., additional, Ray, David, additional, Redder, Ronald J., additional, Rosen, Clifford J, additional, Ross, Nikki, additional, Ruhe, Mark T., additional, Ryzhova, Larisa, additional, Salvador, Ane M., additional, Sedlacek, Radislav, additional, Sharma, Karan, additional, Smith, Chad, additional, Staes, Katrien, additional, Starrs, Lora, additional, Sugiyama, Fumihiro, additional, Takahashi, Satoru, additional, Tanaka, Tomohiro, additional, Trafford, Andrew, additional, Uno, Yoshihiro, additional, Vanhoutte, Leen, additional, Vanrockeghem, Frederique, additional, Willis, Brandon J., additional, Wright, Christian S., additional, Yamauchi, Yuko, additional, Yi, Xin, additional, Yoshimi, Kazuto, additional, Zhang, Xuesong, additional, Zhang, Yu, additional, Ohtsuka, Masato, additional, Das, Satyabrata, additional, Garry, Daniel J., additional, Hochepied, Tino, additional, Thomas, Paul, additional, Parker-Thornburg, Jan, additional, Adamson, Antony D, additional, Yoshiki, Atsushi, additional, Schmouth, Jean-Francois, additional, Golovko, Andrei, additional, Thompson, William R., additional, Lloyd, KC. Kent, additional, Wood, Joshua A., additional, Cowan, Mitra, additional, Mashimo, Tomoji, additional, Mizuno, Seiya, additional, Zhu, Hao, additional, Kasparek, Petr, additional, Liaw, Lucy, additional, Miano, Joseph M., additional, and Burgio, Gaetan, additional

Published
2018
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31. A mutation in transcription factor MAFB causes Focal Segmental Glomerulosclerosis with Duane Retraction Syndrome

Author

Sato, Yoshinori, primary, Tsukaguchi, Hiroyasu, additional, Morita, Hiroyuki, additional, Higasa, Koichiro, additional, Tran, Mai Thi Nhu, additional, Hamada, Michito, additional, Usui, Toshiaki, additional, Morito, Naoki, additional, Horita, Shoichiro, additional, Hayashi, Takao, additional, Takagi, Junko, additional, Yamaguchi, Izumi, additional, Nguyen, Huan Thanh, additional, Harada, Masayo, additional, Inui, Kiyoko, additional, Maruta, Yuichi, additional, Inoue, Yoshihiko, additional, Koiwa, Fumihiko, additional, Sato, Hiroshi, additional, Matsuda, Fumihiko, additional, Ayabe, Shinya, additional, Mizuno, Seiya, additional, Sugiyama, Fumihiro, additional, Takahashi, Satoru, additional, and Yoshimura, Ashio, additional

Published
2018
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35. Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.

Author

Kida, Taiki, Ayabe, Shinya, Omori, Keisuke, Nakamura, Tatsuro, Maehara, Toko, Aritake, Kosuke, Urade, Yoshihiro, and Murata, Takahisa

Subjects
*PULMONARY fibrosis treatment, *PULMONARY fibrosis, *PNEUMONIA, *BLEOMYCIN, *PROSTAGLANDINS, *IMMUNOSTAINING, *GENETICS
Abstract

Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Published
2016
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36. Prostaglandin D2 induces contraction via thromboxane A2 receptor in rat liver myofibroblasts

Author

Maruyama, Tomoharu, Murata, Takahisa, Ayabe, Shinya, Hori, Masatoshi, and Ozaki, Hiroshi

Subjects
*PROSTANOIDS, *EXTRACELLULAR matrix proteins, *CONNECTIVE tissues, *T cells
Abstract

Abstract: Increased intrahepatic resistance is one of the major characteristics of cirrhotic liver, in which extravascular cells including liver myofibroblasts (MFs) abnormally contract. Although several studies provided evidence that various prostaglandins (PG) are involved in liver cirrhosis, the role of PGD2 remains unknown. In this study, we investigated the effect of PGD2 on the contractile properties of liver MFs. Cultured rat liver MFs were used at passages 4–7. A collagen gel contraction assay was used for the evaluation of the MFs contraction. mRNA expression was assessed by semi-quantitative RT-PCR. Intracellular Ca2+ concentrations ([Ca2+]i) were measured by monitoring the fluorescence intensity of fura-2. PGD2 (1–10 μM) induced liver MF contraction in a dose-dependent manner with [Ca2+]i elevation. Pretreatment with 300 nM LaCl3, a nonselective Ca2+ channel blocker abolished the 10 μM PGD2-induced MFs contraction. RT-PCR revealed that three distinct PGD2 responsive receptors, prostanoid DP receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and thromboxane A2 receptor (prostanoid TP receptor), were expressed in liver MFs. While prostanoid DP receptor agonist and CRTH2 agonist didn''t induce contraction, 0.01–1 μM U46619 (11α, 9α-epoxymethano-PGH2, prostanoid TP receptor agonist) caused robust contraction with [Ca2+]i elevation. Furthermore, pretreatment with prostanoid TP receptor antagonists ramatroban (1 μM) or SQ29548 ([1S-[1α, 2α(Z), 3α, 4α]]-7-[3-[[2-[(phenyl amino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid, 1 μM) completely suppressed PGD2-induced contraction and [Ca2+]i elevation. Additionally, we observed that BW245C (1–10 μM) decreased basal MF contraction. These results suggest that PGD2 induces rat liver MF contraction with an increase in [Ca2+]i through prostanoid TP receptor. [Copyright &y& Elsevier]

Published
2008
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37. Generation of B6-Ddx4 em1(CreERT2)Utr , a novel CreERT2 knock-in line, for germ cell lineage by CRISPR/Cas9.

Author

Le HT, Hasegawa Y, Daitoku Y, Kato K, Miznuo-Iijima S, Dinh TTH, Kuba Y, Osawa Y, Mikami N, Morimoto K, Ayabe S, Tanimoto Y, Murata K, Yagami KI, Takahashi S, Mizuno S, and Sugiyama F

Subjects
Animals, DEAD-box RNA Helicases metabolism, Female, Germ Cells cytology, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Integrases metabolism, Male, Mice, Mice, Inbred C57BL, Promoter Regions, Genetic, Cell Lineage, DEAD-box RNA Helicases genetics, Gene Knock-In Techniques methods, Germ Cells metabolism, Integrases genetics
Abstract

Germ cell development is essential for maintaining reproduction in animals. In postpubertal females, oogenesis is a highly complicated event for producing fertilizable oocytes. It starts when dormant primordial oocytes undergo activation to become growing oocytes. In postpubertal males, spermatogenesis is a differentiation process for producing sperm from spermatogonial stem cells. To obtain full understanding of the molecular mechanisms underlying germ cell development, the Cre/loxP system has been widely applied for conditional knock-out mouse studies. In this study, we established a novel knock-in mouse line, B6-Ddx4 em1(CreERT2)Utr , which expresses CreERT2 recombinase under the control of the endogenous DEAD-box helicase 4 (Ddx4) gene promoter. Ddx4 was specifically expressed in both female and male germ cell lineages. We mated the CreERT2 mice with R26GRR mice, expressing enhanced green fluorescent protein (EGFP) and tDsRed before and after Cre recombination. We found tDsRed signals in the testes and ovaries of tamoxifen-treated B6-Ddx4 em1(CreERT2)Utr ::R26GRR mice, but not in untreated mice. Immunostaining of their ovaries clearly showed that Cre recombination occurred in all oocytes at every follicle stage. We also found 100% Cre recombination efficiency in male germ cells via the progeny test. In summary, our results indicate that B6-Ddx4 em1(CreERT2)Utr is beneficial for studying female and male germ cell development., (© 2020 Wiley Periodicals, Inc.)

Published
2020
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