In two hereditary syndromes of the dog, Mullerian ducts persist in the presence of testicular tissue: XX sex reversal and Persistent Mullerian Duct Syndrome (PMDS). The objective of this project is to determine whether the lack of Mullerian duct regression in these animal models of human intersexuality is the result of a deficiency in Mullerian Inhibiting Substance (MIS). If so, these will be the first defined genetic defects in the as yet poorly understood MIS system. Dogs with XX sex reversal and PMDS will be produced by breeding known carriers. The MIS activity of gonads from affected pups will be compared with that of gonads from normal male littermates using a graded organ culture assay for MIS. Results from MIS assays will be examined with respect to gonadal structure, particularly the morphology of Sertoli cells, using light and electron microscopy.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD019393-02
Application #
3316643
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Meyers-Wallen, V N (2012) Gonadal and sex differentiation abnormalities of dogs and cats. Sex Dev 6:46-60
Meyers-Wallen, V N (2009) Review and update: genomic and molecular advances in sex determination and differentiation in small animals. Reprod Domest Anim 44 Suppl 2:40-6
Wu, Xiufeng; Wan, Shengqin; Pujar, Shashikant 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 30:46-56
Pujar, S; Meyers-Wallen, V N (2009) A molecular diagnostic test for persistent Mullerian duct syndrome in miniature schnauzer dogs. Sex Dev 3:326-8
Meyers-Wallen, V N; Hurtgen, J; Schlafer, D et al. (1997) Sry-negative XX true hermaphroditism in a Pasa Fino horse. Equine Vet J 29:404-8
Meyers-Wallen, V N; Palmer, V L; Acland, G M et al. (1995) Sry-negative XX sex reversal in the American cocker spaniel dog. Mol Reprod Dev 41:300-5
Meyers-Wallen, V N; Bowman, L; Acland, G M et al. (1995) Sry-negative XX sex reversal in the German shorthaired pointer dog. J Hered 86:369-74
Meyers-Wallen, V N; Lee, M M; Manganaro, T F et al. (1993) Mullerian inhibiting substance is present in embryonic testes of dogs with persistent mullerian duct syndrome. Biol Reprod 48:1410-8
Sommer, M M; Meyers-Wallen, V N (1991) XX true hermaphroditism in a dog. J Am Vet Med Assoc 198:435-8
Meyers-Wallen, V N; Manganaro, T F; Kuroda, T et al. (1991) The critical period for mullerian duct regression in the dog embryo. Biol Reprod 45:626-33

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