splicing defect in dogs with lethal acrodermatitis

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Lethal acrodermatitis (LAD) is an autosomal recessive hereditary disease in dogs. It is characterized by poor growth, immune deficiency and characteristic skin lesions of the paws and of the face. We mapped the LAD locus to a ~1.11 Mb segment on canine chromosome 14. Whole genome sequence data of an LAD affected dog and 191 controls revealed a candidate causative variant in the MKLN1 gene, encoding muskelin 1. The identified variant, a single nucleotide substitution, MKLN1:c.400+3A>C, altered the 5’-splice site at the beginning of intron 4. We experimentally confirmed that this variant leads to complete skipping of exon 4 in the MKLN1 mRNA in skin. Various cellular functions have been postulated for muskelin 1 including roles in intracellular transport processes, cell morphology, cell spreading, and cell adhesion. Our data from dogs reveal a novel in vivo role for muskelin 1 that is related to the immune system and skin. MKLN1 thus represents a novel candidate gene for human patients with unsolved acrodermatitis and/or immune deficiency phenotypes. LAD affected dogs may serve as models to gain more insights into the function of muskelin 1.

Vyšlo v časopise: splicing defect in dogs with lethal acrodermatitis. PLoS Genet 14(3): e32767. doi:10.1371/journal.pgen.1007264
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1007264

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