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Canine Persistent Müllerian Duct Syndrome (PMDS)
| Acronym: | PMDS |
| Gene: | AMHR2 |
| Mutation: | c.262C>T |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Canine Persistent Müllerian Duct Syndrome (PMDS) is a form of male pseudohermaphroditism, an inherited disorder of sexual development, affecting the Miniature Schnauzer dog. The disorder is characterized by the presence of Mullerian ducts, such as the uterus, Fallopian tubes, and upper vagina, while the external genitalia appears normal on the affected dogs. PMDS has been reported in Miniature Schnauzers in Northern America, Europe, and Asia. This canine disorder shares characteristics with its human equivalent of PMDS, which makes it an important animal model for the disease’s study. During embryonic development, Mullerian ducts regress shortly after the development of the testes, which is induced by the working of two distinct hormones produced by the fetal testes. Those hormones are testosterone, produced by Leydig cells, and anti-Mullerian hormone (AMH), secreted by Sertoli cells. Testosterone mediates the action necessary for the prostate formation and masculinization of the external genitalia, while AHM is responsible for the regression of Mullerian structures. In case of mutation in the AHM gene, failure of regression of Mullerian structures will occur.
PMDS-affected Miniature Schnauzers are male dogs with normal karyotype, 78 XY. They have a normal male phenotype and complete male internal genitalia, including vasa deferentia, and prostate, but internally Mullerian and Wolffian duct system is present. All layers of the uterus are present, although they lack ovarian hormonal stimulation. Approximately 50% of affected dogs are either unilaterally or bilaterally cryptorchid and are lacking one or both testes from the scrotum. Histological examination of cryptorchid testes in PMDS dogs reveals the absence of germ cells. Affected dogs with bilateral scrotal testes are fertile, but their sperm counts are lower than expected for the body weight. Dogs with bilateral cryptorchidism are sterile, while PMDS males with unilateral cryptorchidism are subfertile and with lower sperm counts than in unaffected dogs with similar body weight. Older PMDS dogs with cryptorchidism are often affected with Sertoli cell tumor, as well as pyometra (uterine infection), urinary obstruction, and urogenital tract infections.
Persistent Müllerian Duct Syndrome Miniature Schnauzer Type is caused by a mutation of the AMHR2 gene, also known as the MISRII gene (Mullerian inhibiting substance type II receptor). The mutation causes the expression of a truncated protein, which results in the failure of regression of Mullerian structures. The disorder is inherited as an autosomal recessive disorder but affects only male dogs, which makes it sex-limited. A dog can be clear, carrier, and affected. Affected can be only male dogs, while carriers can be both male and female dogs. When mating two carrier dogs, there is a 25% chance of obtaining an affected puppy. Since affected dogs may appear as normal externally and still be fertile, genetic testing is highly recommendable in order to eliminate the mutation from the dog breed.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Wu X, Wan S, Pujar S, Haskins ME, Schlafer DH, Lee MM, Meyers-Wallen VN. A single base pair mutation encoding a premature stop codon in the MIS type II receptor is responsible for canine persistent Müllerian duct syndrome. J Androl. 2009 Jan-Feb; 30(1):46-56.
Wu, X., Wan, S. et al (2009.): A Single Base Pair Mutation Encoding a Premature Stop Codon in the MIS type II receptor is Responsible for Canine Persistent Müllerian Duct Syndrome. J Androl. 2009 ; 30(1): 46–56. doi:10.2164/jandrol.108.005736.
Vegter, AR., Kooistra, HS., Sluijs,van FJ (2010): Persistent Mullerian Duct Syndrome in a Miniature Schnauzer Dog with Signs of Feminization and a Sertoli Cell Tumor. Reprod Dom Anim 45, 447–452 (2010); doi: 10.1111/j.1439-0531.2008.01223