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A spontaneous, autosomal, recessive mutation called witch nails (<jats:italic>whnl<\/jats:italic>) is described here where the distal nail matrix and nail bed undergo degenerative changes resulting in formation of an abnormal nail plate causing mice to develop long, curved nails. This mutation arose spontaneously in a colony of MRL\/MpJ-<jats:italic>Fas<\/jats:italic><jats:sup><jats:italic>lpr<\/jats:italic><\/jats:sup>\/J at The Jackson Laboratory. Homozygous mutant mice are recognizable by 8 weeks of age by their long, curved nails. The <jats:italic>whnl<\/jats:italic> mutation, mapped on Chromosome 15, is due to a 7-bp insertion identified in the 3\u2019 region of exon 9 in the <jats:italic>Krt90<\/jats:italic> gene (formerly Riken cDNA <jats:italic>4732456N10Rik<\/jats:italic>), and is predicted to result in a frameshift that changes serine 476 to arginine and subsequently introduces 36 novel amino acids into the protein before a premature stop codon (p. Ser476ArgfsTer36). By immunohistochemistry the normal KRT90 protein is expressed in the nail matrix and nail bed in control mice where lesions are located in mutant mice. Immunoreactivity toward equine KRT124, the ortholog of mouse KRT90, is restricted to the hoof lamellae (equine hoof wall and lamellae are homologous to the mouse nail plate and nail bed) and the mouse nail bed. Equine laminitis lesions are similar to those observed in this mutant mouse suggesting that the latter may be a useful model for hoof and nail diseases. This first spontaneous mouse mutation affecting the novel <jats:italic>Krt90<\/jats:italic> gene provides new insight into the normal regulation of the molecular pathways of nail development.<\/jats:p>","DOI":"10.1371\/journal.pone.0277284","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T18:24:36Z","timestamp":1668450276000},"page":"e0277284","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Witch Nails (Krt90whnl): A spontaneous mouse mutation affecting nail growth and development"],"prefix":"10.1371","volume":"17","author":[{"given":"John P.","family":"Sundberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1435-100X","authenticated-orcid":true,"given":"Hannah","family":"Galantino-Homer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Fairfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia F.","family":"Ward-Bailey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belinda S.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Berry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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