Naked (N) mutant mice carry a nonsense mutation in the homeobox of Hoxc13. Issue 3 (25th October 2021)

• Record Type: Journal Article
• Authors: Perez, Carlos J.; Mecklenburg, Lars; Fernandez, Almudena; Cantero, Marta; de Souza, Tiago Antonio; Lin, Kevin; Dent, Sharon Y. R.; Montoliu, Lluis; Awgulewitsch, Alexander; Benavides, Fernando
• Is Part Of: Experimental dermatology. Volume 31:Issue 3(2022)
• Page Start: 330
• Page End: 340
• Publication Date: 2021-10-25
• Subjects: animal model -- hair follicle -- mice; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.14469
• Languages: English
• ISSNs: 0906-6705

Abstract

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.