Search

Two siblings with yellow nail syndrome and mental retardation are described. In addition to nail changes, the younger brother was found to have congenital lymphoedema and idiopathic pleural effusion, and the elder brother, lymphoedema praecox. They had in common a history of respiratory tract infections. Their intelligence quotient as measured by the Suzuki-Binet tests was 30% and 70% respectively. [ABSTRACT FROM AUTHOR]

An abstract of the study "Production of Genetically Modified Pigs by Artificial Reproductive Technologies Using Frozen Epididymal Sperm," by K. Honda and colleagues is presented.

Development of specially designed pigs for basic research and preclinical application of xenotransplantation relies on highly sophisticated animal biotechnologies such as somatic cell cloning and genetic engineering. We have been developing two major technologies, i.e. somatic cell cloning and intracytoplasmic sperm injection (ICSI)-mediated gene transfer, aiming at improving production efficiency of genetically modified pigs. We have produced genetically modified pigs by heterozygous knock-out of α(1,3)-galactosyltransferase gene (GalT-KO) and co-expression of two transgenes, human decay-accelerating factor (hDAF) and N-acetylglucosaminyltransferase III (GntIII), using the technology of somatic cell nuclear transfer (SCNT) [1]. Cells collected from these pigs were used to generate homozygous GalT-KO cells by means of spontaneous mutation phenomenon of heterozygous GalT-KO cells during cultivation, i.e. loss of heterozygosity. Then homozygous GalT-KO pigs have been successfully cloned by SCNT [2]... [ABSTRACT FROM AUTHOR]

An abstract of the study "Generation of a Double-Transgenic Pig With Pancreas-Specific Green and Liver-Specific Red Fluorescence," by H. Matsunari and colleagues is presented.

An abstract of the study "Production of Chimeric Porcine Fetuses by Aggregation Method Using Parthenogenetic Embryos," by K. Nakanos and colleagues is presented.

An abstract of the study "A Hollow Fiber Vitrification Method Enables Cryobanking of In Vitro-Maturation/In Vitro-Fertilization-Derived Transgenic Pig Embryos," by M. Maehara et al, is presented.

Background: To overcome organ shortage during transplantation, interspecies organ generation via blastocyst complementation has been proposed, although not yet in evolutionarily distant species. To establish high levels of chimerism, low chimerism is required early in development, followed by high chimerism, to effectively complement the organ niche. Very few human cells are expected to contribute to chimerism in heterologous animals. Previous studies had demonstrated increased donor chimerism in both intra- and interspecies chimeras in rodents, using insulin-like growth factor 1 receptor ( Igf1r ) knockout (KO) mice; deletion of the Igf1r gene in the mouse host embryo created a cell-competitive niche. The current study aimed to generate IGF1R- KO pigs and evaluate whether they have the same phenotype as Igf1r -KO mice., Methods: To generate IGF1R- KO pigs, genome-editing molecules were injected into the cytoplasm of pig zygotes. The fetuses were evaluated at 104 days of gestation., Results: IGF1R -KO pigs were generated successfully. Their phenotypes were almost identical to those of Igf1r -KO mice, including small lungs and enlarged endodermal organs in fetuses, and they were highly reproducible., Conclusions: Pigs may allow the generation of organs using blastocyst complementation with developmentally-compatible xenogeneic pluripotent stem cells over a large evolutionary distance., Competing Interests: H.Nagashima is a founder and shareholder of PorMedTec Co., Ltd. These associations do not alter the authors' adherence to the journal's policies on sharing data and materials. The other authors declare that they have no conflicts of interest., (© 2024 The Author(s).)

Inherited retinal dystrophies (IRDs) are progressive diseases leading to vision loss. Mutation in the eyes shut homolog (EYS) gene is one of the most frequent causes of IRD. However, the mechanism of photoreceptor cell degeneration by mutant EYS has not been fully elucidated. Here, we generated retinal organoids from induced pluripotent stem cells (iPSCs) derived from patients with EYS-associated retinal dystrophy (EYS-RD). In photoreceptor cells of RD organoids, both EYS and G protein-coupled receptor kinase 7 (GRK7), one of the proteins handling phototoxicity, were not in the outer segment, where they are physiologically present. Furthermore, photoreceptor cells in RD organoids were vulnerable to light stimuli, and especially to blue light. Mislocalization of GRK7, which was also observed in eys-knockout zebrafish, was reversed by delivering control EYS into photoreceptor cells of RD organoids. These findings suggest that avoiding phototoxicity would be a potential therapeutic approach for EYS-RD.

There have been high expectations in recent years of using xenotransplantation and regenerative medicine to treat humans, and pigs have been utilized as the donor model. Pigs used for these clinical applications must be microbiologically safe, that is, free of infectious pathogens, to prevent infections not only in livestock, but also in humans. Currently, however, the full spectrum of pathogens that can infect to the human host or cause disease in transplanted porcine organs/cells has not been fully defined. In the present study, we thus aimed to develop a larger panel for the detection of pathogens that could potentially infect xenotransplantation donor pigs. Our newly developed panel, which consisted of 76 highly sensitive PCR detection assays, was able to detect 41 viruses, 1 protozoa, and a broad range of bacteria (by use of universal 16S rRNA primers). The applicability of this panel was validated using blood samples from uterectomy-born piglets, and pathogens suspected to be vertically transmitted from sows to piglets were successfully detected. We estimate that, at least for viruses and bacteria, the number of target pathogens detected by the developed screening panel should suffice to meet the microbiological safety levels required worldwide for xenotransplantation and/or regenerative therapy. This panel provides greater diagnosis options to produce donor pigs so that it would render unnecessary to screen for all pathogens listed. Instead, the new panel could be utilized to detect only required pathogens within a given geographic range where the donor pigs for xenotransplantation have been and/or are being developed., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disorder caused by mutation in the dystrophin gene ( DMD ) on the X chromosome. Female DMD carriers occasionally exhibit symptoms such as muscle weakness and heart failure. Here, we investigated the characteristics and representativeness of female DMD carrier ( DMD- X KO X WT ) pigs as a suitable disease model., Methods: In vitro fertilization using sperm from a DMD -X KO Y↔X WT X WT chimeric boar yielded DMD- X KO X WT females, which were used to generate F2 and F3 progeny, including DMD- X KO X WT females. F1-F3 piglets were genotyped and subjected to biochemical analysis for blood creatine kinase (CK), aspartate aminotransferase, and lactate dehydrogenase. Skeletal muscle and myocardial tissue were analyzed for the expression of dystrophin and utrophin, as well as for lymphocyte and macrophage infiltration., Results: DMD -X KO X WT pigs exhibited various characteristics common to human DMD carrier patients, namely, asymptomatic hyperCKemia, dystrophin expression patterns in the skeletal and cardiac muscles, histopathological features of skeletal muscle degeneration, myocardial lesions in adulthood, and sporadic death. Pathological abnormalities observed in the skeletal muscles in DMD -X KO X WT pigs point to a frequent incidence of pathological abnormalities in the musculoskeletal tissues of latent DMD carriers. Our findings suggest a higher risk of myocardial abnormalities in DMD carrier women than previously believed., Conclusions: We demonstrated that DMD- X KO X WT pigs could serve as a suitable large animal model for understanding the pathogenic mechanism in DMD carriers and developing therapies for female DMD carriers., Competing Interests: H.N. is a founder and shareholder of PorMedTec Co., Ltd. These associations do not alter the authors' adherence to the journal's policies on sharing data and materials. The other authors declare that they have no conflicts of interest., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Mammalian artificial chromosomes have enabled the introduction of extremely large amounts of genetic information into animal cells in an autonomously replicating, nonintegrating format. However, the evaluation of human artificial chromosomes (HACs) as novel tools for curing intractable hereditary disorders has been hindered by the limited efficacy of the delivery system. We generated dystrophin gene knockout ( DMD -KO) pigs harboring the HAC bearing the entire human DMD via a somatic cell cloning procedure (DYS-HAC-cloned pig). Restored human dystrophin expression was confirmed by immunofluorescence staining in the skeletal muscle of the DYS-HAC-cloned pigs. Viability at the first month postpartum of the DYS-HAC-cloned pigs, including motor function in the hind leg and serum creatinine kinase level, was improved significantly when compared with that in the original DMD -KO pigs. However, decrease in systemic retention of the DYS-HAC vector and limited production of the DMD protein might have caused severe respiratory impairment with general prostration by 3 months postpartum. The results demonstrate that the use of transchromosomic cloned pigs permitted a straightforward estimation of the efficacy of the DYS-HAC carried in affected tissues/organs in a large-animal disease model, providing novel insights into the therapeutic application of exogenous mammalian artificial chromosomes., Competing Interests: H.N. is a founder and shareholder of PorMedTec Co., Ltd. These associations do not alter the authors’ adherence to the journal’s policies on sharing data and materials., (© 2023 The Authors.)

Amyotrophic lateral sclerosis (ALS) causes progressive degeneration of the motor neurons. In this study, we delivered the genetic construct including the whole locus of human mutant superoxide dismutase 1 (SOD1) with the promoter region of human SOD1 into porcine zygotes using intracytoplasmic sperm injection-mediated gene transfer, and we thereby generated a pig model of human mutant SOD1-mediated familial ALS. The established ALS pig model exhibited an initial abnormality of motor neurons with accumulated misfolded SOD1. The ALS pig model, with a body size similar to that of human beings, will provide opportunities for cell and gene therapy platforms in preclinical translational research., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Recent developments in reproductive biology have enabled the generation of genetically engineered pigs as models for inherited human diseases. Although a variety of such models for monogenic diseases are currently available, reproduction of human diseases caused by haploinsufficiency remains a major challenge. The present study compares the phenotypes of mouse and pig models of Marfan syndrome (MFS), with a special focus on the expressivity and penetrance of associated symptoms. Furthermore, investigation of the gene regulation mechanisms associated with haploinsufficiency will be of immense utility in developing faithful MFS pig models.