We seek to understand molecular events involved in the differentiation of the mammalian male embryonic gonad. Such knowledge should be of benefit for improved diagnosis, and possibly prenatal diagnosis, of human intersex conditions as well as increasing our understanding of normal human development. Our studies will use both mouse models and human material. Studies in mice will focus on genetic loci in the proximal arm of chromosome 17 which interact with the mouse Y chromosome (which also has variants) to try and elucidate how these autosomal loci interact with the Y chromosome and other autosomal loci in contributing to normal testicular development. Among the loci on chromosome 17 may be those containing Banded krait minor satellite (Bkm) sex specific sequences. Since certain large deletions (T-Or1 and T-Hp) in this area of chromosome 17 can cause hermaphroditism, we will determine whether or not these deletions alter the amounts of Bkm-sequences detected on chromosome 17 by in situ hybridization. We will use the Bkm probe to look for mRNAs containing Bkm sequences in mouse and human fetal gonads and appropriate other tissues. Cosmid clones from the proximal region of mouse chromosome 17 and lambda clones from the human X chromosome will be screened with a Bkm probe. Subportions of positive clones will be used to screen fetal gonad RNA. The human Y chromosomal clones previously obtained, and new ones obtained by PERT and chromosome """"""""hop"""""""" techniques, will be used to study XX males and their parents in an attempt to determine the source of the Y chromosomal DNA usually found in such XX males. The work on human material will also use human Y chromosome clones to look for expressed Y sequences in the male fetal gonad. Genomic clones corresponding to mouse or human male fetal gonad specific expressed sequences will be sought by screening cDNA libraries with the identified probe and using the cDNA clone to screen genomic clones (when the probe is not unique sequence).

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD020670-01A1
Application #
3319000
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Erickson, R P (1997) Does sex determination start at conception? Bioessays 19:1027-32
Zwingman, T; Fujimoto, H; Lai, L W et al. (1994) Transcription of circular and noncircular forms of Sry in mouse testes. Mol Reprod Dev 37:370-81
Seaver, L H; Grimes, J; Erickson, R P (1994) Female pseudohermaphroditism with multiple caudal anomalies: absence of Y-specific DNA sequences as pathogenetic factors. Am J Med Genet 51:16-21
Ao, A; Erickson, R P; Stalvey, J R (1993) Sites of transcription of the Mullerian inhibiting substance gene in mouse testis. Mol Reprod Dev 35:159-64
Zwingman, T; Erickson, R P; Boyer, T et al. (1993) Transcription of the sex-determining region genes Sry and Zfy in the mouse preimplantation embryo. Proc Natl Acad Sci U S A 90:814-7
Erickson, R P; Zwingman, T; Ao, A (1993) Gene expression, X-inactivation, and methylation during spermatogenesis: the case of Zfa, Zfx, and Zfy in mice. Mol Reprod Dev 35:114-20
Van Dyke, D L; Wiktor, A; Palmer, C G et al. (1992) Ullrich-Turner syndrome with a small ring X chromosome and presence of mental retardation. Am J Med Genet 43:996-1005
Graves, P E; Erickson, R P (1992) An amino acid change in the DNA-binding region of Sry, found in Mus musculus domesticus and other species, does not explain C57BL/6J-YDOM sex-reversal. Biochem Biophys Res Commun 185:310-6
Bailey, W A; Zwingman, T A; Reznik, V M et al. (1992) End-stage renal disease and primary hypogonadism associated with a 46,XX karyotype. Am J Dis Child 146:1218-23
Erickson, R P; Glover, T W; Hall, B K et al. (1991) Polymerase chain reactions with alphoid-repeat primers in combination with Alu or LINEs primers, generate chromosome-specific DNA fragments. Ann Hum Genet 55:199-211

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