Disease relevance of Tp(Y)1Ct

• Sex reversed mice heterozygous for testicular feminization are genetic females which are converted to males by the autosomal Sxr ("sex reversed") mutation, thus imitating the Y-chromosome [1].

High impact information on Tp(Y)1Ct

• The conserved nucleotide sequences of Bkm, which define Sxr in the mouse, are transcribed [2].
• Satellite DNA (Bkm) from the W sex-determining chromosome of snakes, which is related to sequences on the mouse Y chromosome, has been used to analyze the DNA and chromosomes of sex-reversed (Sxr) XXSxr male mice [3].
• Meitoic crossing-over between the X and Y chromosomes of male mice carrying the sex-reversing (Sxr) factor [4].
• Zfy-1 alone may suffice to determine maleness; Zfy-2 is dispensable, as it was deleted in an Sxr variant that retains sex-determining function but has lost other genes [5].
• The original sex-reversed females appeared among the offspring of XY males that carried the Yp duplication Sxr on their X chromosome [6].

Biological context of Tp(Y)1Ct

• A structural analysis of the Sxr region of the mouse Y chromosome [7].
• T-cell and antibody typing of a mouse population segregating for Sxr and H-2 haplotype [8].
• DNA fingerprinting revealed that the banding pattern characteristic of Sxr' had been replaced by the pattern associated with the native testis-determining region of the normal Y chromosome of that stock, presumably by pairing and crossing-over between the two testis-determining regions of the father's Y Sxr' chromosome [9].
• Also, we show that intrachromosomal recombination between the Y short arm and Sxr' can sometimes occur during male meiosis, restoring the deleted DNA sequences and resulting in an H-Y+ mouse (male 719 in this paper) [10].
• Spy is present in the Y-derived Sxr fragment so XOSxr germ cells enter meiosis normally [11].

Anatomical context of Tp(Y)1Ct

• Using Northern blots to analyse RNA isolated from the testes of mutant mice (Tfm/Y and Sxr/+) blocked at specific stages in spermatogenesis or RNA from sexually immature mice, 8 clones have been identified which correspond to RNAs expressed uniquely or at much higher levels in meiotic or post meiotic cells [12].
• Univalent X and Y chromosomes were observed to undergo self-association in a variable proportion of spermatocytes of all Sxr-carrying males [13].
• Evidence for a defective seminiferous tubule barrier in testes of Tfm and Sxr mice [14].
• The finding that X/X, Sxr/+ germ cells can produce fully functional oocytes has implications for the function of the Sex-reversed gene, the control of germ cell differentiation, and the role of germ cells in primary sex determination [15].
• Sxr is known to affect spermatogenesis and Sertoli cells [16].

Associations of Tp(Y)1Ct with chemical compounds

• The corresponding sucrose space in testes from Tfm/Y and Sxr/+ sterile mutants was elevated to 57.7% and 52.0%, respectively [14].
• Testes from X/X Sxr mice secreted more (P less than 0.05) dehydroepiandrosterone and androstenedione than X/Y mouse testes [17].
• We determined the impact that the absence of an intact Y chromosome has on Leydig cell function by comparing the steroid secretion profiles of in vitro perfused testes from X/X Sxr and X/Y mice [17].
• The activities of phosphoglycerate kinase B and lactate dehydrogenase C4 were correlated with the state of spermatogenesis in testes of sex-reversed (Sxr) mice [18].
• Injection of human chorionic gonadotrophin (hCG) increased intratesticular testosterone in Sxr males more than in normal males although there was no difference in serum testosterone levels [19].

Enzymatic interactions of Tp(Y)1Ct

• Hya and Spy map to DNA deleted from the Sxr region in the deletion variant Sxrb (the delta Sxrb DNA) [7].

Other interactions of Tp(Y)1Ct

• Our data is in contrast to a recent report of a recombination frequency separating Sts and Sxr of as high as 6.2-9.8% [20].
• Moreover, the mutation is complemented by Sxr', the minimum portion of the mouse Y known to carry Tdy [21].

Analytical, diagnostic and therapeutic context of Tp(Y)1Ct

• The possibility that hormonal differences could instead be responsible for the lower activity in females was ruled out by the findings that (a) castration of males did not reduce their STS levels and (b) sex-reversed males, X/X Sxr, had STS levels typical of females [22].
• We now demonstrate the presence of chromosome Y-related DNA sequences on proximal chromosome 17 in Sex-reversed (Sxr) and normal mice using in situ hybridization of mitotic chromosomes with 3H-labelled pCS316 (ref. 4), a probe that shows major hybridization to the proximal portion of the mouse chromosome Y [23].
• Total mouse Y-chromosome libraries were constructed from flow-sorted material and a Sxr regional library after specific microdissection and cloning [24].
• One clone from each family was chosen for detailed analysis by Southern blot hybridization, polymerase chain reaction (PCR) on normal and aberrant genomes (Sxr), and fluorescence in situ hybridization [25].
• Previous work has established that whereas X/X mice carrying the sex-reversing chromosomal fragment Sxr are positive for the male-specific transplantation antigen, H-Y, X/X mice carrying the variant Sxr', although they too develop as phenotypic males, are H-Y negative [26].

References