title: Generation of Hoxc13 knockout pigs recapitulates human ectodermal dysplasia-9.
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.
authors.affiliation: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Liuping
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Bentian
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiaoshuai
authors.initials: X
authors.lastname: Ren
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Chengdan
authors.initials: C
authors.lastname: Lai
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Kepin
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Kang
authors.initials: K
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Lai
authors.affiliation: Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Nana
authors.initials: N
authors.lastname: Fan
mesh_terms: D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D064113:CRISPR-Cas Systems; D004195:Disease Models, Animal; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology*; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D013552:Swine
chemical_list: C410305:HOXC13 protein, human; D018398:Homeodomain Proteins