Faculty, Staff and Student Publications
Publication Date
3-1-2022
Journal
Experimental Dermatology
Abstract
Loss of function mutations in HOXC13 have been associated with Ectodermal Dysplasia-9, Hair/Nail Type (ECTD9) in consanguineous families, characterized by sparse to complete absence of hair and nail dystrophy. Here we characterize the spontaneous mouse mutation Naked (N) as a terminal truncation in the Hoxc13 (homeobox C13) gene. Similar to previous reports for homozygous Hoxc13 knock-out (KO) mice, homozygous N/N mice exhibit generalized alopecia with abnormal nails and a short lifespan. However, in contrast to Hoxc13 heterozygous KO mice, N/+ mice show generalized or partial alopecia, associated with loss of hair fibres, along with normal lifespan and fertility. Our data point to a lack of nonsense-mediated Hoxc13 transcript decay and the presence of the truncated mutant protein in N/N and N/+ hair follicles, thus suggesting a dominant-negative mutation. To our knowledge, this is the first report of a semi-dominant and potentially dominant-negative mutation affecting Hoxc13/HOXC13. Furthermore, recreating the N mutant allele in mice using CRISPR/Cas9-mediated genome editing resulted in the same spectrum of deficiencies as those associated with the spontaneous Naked mutation, thus confirming that N is indeed a Hoxc13 mutant allele. Considering the low viability of the Hoxc13 KO mice, the Naked mutation provides an attractive new model for studying ECTD9 disease mechanisms.
Keywords
Alopecia, Animals, Codon, Nonsense, Ectodermal Dysplasia, Genes, Homeobox, Homeodomain Proteins, Humans, Mice, Mutation, Nail Diseases, Transcription Factors, Animal Model, Hair Follicle, Mice
DOI
: 10.1111/exd.14469
PMID
34657330
PMCID
PMC11892394
PubMedCentral® Posted Date
3-10-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Dermatology Commons, Medical Sciences Commons, Oncology Commons