Title
A single base pair mutation encoding a premature stop codon in the MIS type II receptor is responsible for canine persistent Mullerian duct syndrome
PubMed ID
18723470
UMMS Affiliation
Department of Cell Biology; Department of Pediatrics
Date
1-30-2009
Document Type
Article
Subjects
Amino Acid Sequence; Animals; Base Sequence; Codon, Nonsense; DNA Mutational Analysis; Dogs; Genes, Recessive; Genitalia; Gonadal Dysgenesis; Male; Molecular Sequence Data; Pedigree; Phenotype; Point Mutation; Receptors, Peptide; Receptors, Transforming Growth Factor beta
Disciplines
Cell Biology | Life Sciences | Medicine and Health Sciences
Abstract
Mullerian inhibiting substance (MIS), a secreted glycoprotein in the transforming growth factor-beta family of growth factors, mediates regression of the Mullerian ducts during embryonic sex differentiation in males. In persistent Mullerian duct syndrome (PMDS), rather than undergoing involution, the Mullerian ducts persist in males, giving rise to the uterus, fallopian tubes, and upper vagina. Genetic defects in MIS or its receptor (MISRII) have been identified in patients with PMDS. The phenotype in the canine model of PMDS derived from the miniature schnauzer breed is strikingly similar to that of human patients. In this model, PMDS is inherited as a sex-limited autosomal recessive trait. Previous studies indicated that a defect in the MIS receptor or its downstream signaling pathway was likely to be causative of the canine syndrome. In this study, the canine PMDS phenotype and clinical sequelae are described in detail. Affected and unaffected members of this pedigree are genotyped, identifying a single base pair substitution in MISRII that introduces a stop codon in exon 3. The homozygous mutation terminates translation at 80 amino acids, eliminating much of the extracellular domain and the entire transmembrane and intracellular signaling domains. Findings in this model could enable insights to be garnered from correlation of detailed clinical descriptions with molecular defects, which are not otherwise possible in the human syndrome.
Rights and Permissions
Citation: J Androl. 2009 Jan-Feb;30(1):46-56. Epub 2008 Aug 21. Link to article on publisher's site