MLPH Genotype--Melanin Phenotype Correlation in Dilute Dogs

Abstract

Coat color dilution in dogs is a specific pigmentation phenotype caused by a defective transport of melanosomes leading to large clumps of pigment. It is inherited as a Mendelian autosomal recessive trait and may be accompanied by hair loss, the so-called color dilution alopecia (CDA), or black hair follicular dysplasia (BHFD). We previously identified the noncoding c.-22G.A transition in the melanophilin gene (MLPH) as a candidate causative mutation for the dilute phenotype. We have now extended our study and genotyped 935 dogs from 20 breeds segregating for dilute coat color. The dilute-associated A allele segregates in many different breeds suggesting an old mutation event. We also investigated skin biopsies of dogs suspected of having either CDA or BHFD, and our data clearly indicate that the dilute mutation is required but not sufficient to develop clinical signs of the disease. The risk to develop CDA/BHFD seems to be breed specific. Interestingly, 22 out of 29 dogs with clinical signs of CDA/BHFD have clumped melanin in the epidermis, the follicular epithelium, and the hair shafts, whereas in dilute dogs without clinical disease, clumped melanin is only found in the follicular epithelium and the hair shafts but not in the epidermis.