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Generation of Hoxc13 knockout pigs recapitulates human ectodermal dysplasia-9
- Source :
- Human molecular genetics. 26(1)
- Publication Year :
- 2016
-
Abstract
- Atrichia and sparse hair phenotype cause distress to many patients. Ectodermal dysplasia-9 (ED-9) is a congenital condition characterized by hypotrichosis and nail dystrophy without other disorders, and Hoxc13 is a pathogenic gene for ED-9. However, mice carrying Hoxc13 mutation present several other serious disorders, such as skeletal defects, progressive weight loss and low viability. Mouse models cannot faithfully mimic human ED-9. In this study, we generated an ED-9 pig model via Hoxc13 gene knockout through single-stranded oligonucleotides (c.396C > A) combined with CRISPR/Cas9 and somatic cell nuclear transfer. Eight cloned piglets with three types of biallelic mutations (five piglets with Hoxc13c.396C > A/c.396C > A, two piglets with Hoxc13c.396C > A/c.396C > A + 1 and one piglet with Hoxc13Δ40/Δ40) were obtained. Hoxc13 was not expressed in pigs with all three mutation types, and the expression levels of Hoxc13-regulated genes, namely, Foxn1, Krt85 and Krt35, were decreased. The hair follicles displayed various abnormal phenotypes, such as reduced number of follicles and disarrayed hair follicle cable without normal hair all over the body. By contrast, the skin structure, skeleton phenotype, body weight gain and growth of Hoxc13 knockout pigs were apparently normal. The phenotypes of Hoxc13 mutation in pigs were similar to those in ED-9 patients. Therefore, Hoxc13 knockout pigs could be utilized as a model for ED-9 pathogenesis and as a hairless model for hair regeneration research. Moreover, the hairless pigs without other major abnormal phenotypes generated in this study could be effective models for other dermatological research because of the similarity between pig and human skins.
- Subjects :
- 0301 basic medicine
Male
Ectodermal dysplasia
Swine
Biology
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Fetus
Ectodermal Dysplasia
Sequence Homology, Nucleic Acid
Genetics
medicine
Animals
Humans
Molecular Biology
Genetics (clinical)
Gene knockout
Skin
Homeodomain Proteins
Mutation
integumentary system
Base Sequence
Body Weight
General Medicine
Fibroblasts
medicine.disease
Hair follicle
Molecular biology
Phenotype
Hairless
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Hypotrichosis
Female
CRISPR-Cas Systems
Hair Follicle
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14602083
- Volume :
- 26
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Human molecular genetics
- Accession number :
- edsair.doi.dedup.....144acc43fd53658ecc8e431b4950a1ec