A novel spontaneous recessive Kitl mutation causes localized hair graying via loss of follicular melanocyte lineage in mice.

The Kitl/c-Kit signaling axis centrally controls mammalian melanocyte development, survival and cutaneous pigment homeostasis. Most known pathogenic Kitl variants are dominant and usually cause multi-system lesions, with variable phenotypic severity among alleles. Here, we comprehensively characterized a novel spontaneous recessive Kitl mutation in C3H/He mice that induces localized hair graying limited to the forehead, abdomen and paws. Linkage mapping positioned the mutation within a 5.05 Mb interval on chromosome 10, and molecular assays verified an intron 3 IAP retrotransposon insertion driving abnormal splicing and inclusion of a 42-bp cryptic exon. This mutant allele is provisionally designated Kitlm1Yzcm. Mutant hair follicles were morphologically intact yet melanin-free; c-Kit and DCT immunostaining showed undetectable follicular melanocyte lineage signals, suggesting localized hair graying may arise from defective melanoblast colonization or alternative post‑migratory melanocyte defects, rather than impaired melanin synthesis.This novel Kitlm1Yzcmmutant provides a mouse model for investigating mechanisms of localized cutaneous depigmentation and supporting pre‑clinical drug development.