Genetic investigation of the AMH and AMHR2 genes in canine Persistent Müllerian Duct Syndrome

Abstract

Persistent Müllerian duct syndrome (PMDS) is a sex-limited disorder in which male dogs develop portions of the female reproductive tract. Cryptorchidism and its sequelae of infertility and increased risk for testicular cancer are important consequences of PMDS. Anti-Müllerian hormone (AMH) and its receptor induce the regression of the Müllerian ducts in male embryos. The genetic basis for PMDS in Miniature Schnauzers (MS) is an autosomal recessive nonsense mutation in the AMH receptor gene, AMHR2. The objectives of this study were to determine the prevalence of the AMHR2 mutation in MS and whether it was responsible for PMDS in a Belgian Malinois. Such information is crucial to determining the value of genetic testing in MS and would aid development of a genetic test for the Belgian Malinois breed. Allele-specific primers were designed to genotype dogs for the AMHR2 mutation. Genomic DNA of 216 MS (containing one known male PMDS case) and 1 Belgian Malinois (a known male PMDS case) was tested. The MS cohort had a PMDS mutation allele frequency of 16% and a carrier genotypic frequency of 27%. Besides the known affected male MS dog, 1 male and 2 female MS dogs were homozygous for the mutation. These findings support a benefit to testing MS used for breeding for the AMHR2 mutation. The genetic basis for PMDS in the Belgian Malinois was not determined; no coding or splicing mutations were identified in AMH or AMHR2.