Eicher E M, Washburn L L, Schork N J, Lee B K, Shown E P, Xu X, Dredge R D, Pringle M J, Page D C
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Nat Genet. 1996 Oct;14(2):206-9. doi: 10.1038/ng1096-206.
A powerful approach for identifying mammalian primary (gonadal) sex determination genes is the molecular genetic analyses of sex reversal conditions (that is, XX individuals with testicular tissue and XY individuals with ovarian tissue). Here we determined the number and chromosomal location of autosomal and X-linked genes that cause sex reversal in C57BL/6J (B6) mice carrying a Y chromosome of Mus domesticus poschiavinus origin (YPOS). B6 XYPOS mice develop either as females with exclusively ovarian tissue or as true hermaphrodites with ovarian and testicular tissue. In contrast, the YPOS chromosome is fully masculinizing on most other inbred strain backgrounds. B6-YPOS sex reversal appears to result from the incompatibility of the Sry (sex determining region, Y chromosome) allele carried on the YPOS chromosome with B6-derived autosomal or X-linked loci. We found strong evidence for the location of one gene, designated tda1 (testis-determining, autosomal 1), at the distal end of Chromosome (Chr) 4 and a second gene, tda2, in the central region of Chr 2. A third gene, tda3, on Chr 5 is implicated, but the evidence here is not as strong. We suggest that B6 alleles at these loci predispose XYPOS fetuses to ovarian tissue development, but no single locus or combination of loci is necessary and sufficient to cause sex reversal. The TDA proteins may regulate Sry expression or form complexes with the SRY protein to regulate other genes, or the tda genes may be activated or repressed by the SRY protein.
一种鉴定哺乳动物原发性（性腺）性别决定基因的有效方法是对性反转情况进行分子遗传学分析（即具有睾丸组织的XX个体和具有卵巢组织的XY个体）。在这里，我们确定了携带源自波氏小家鼠Y染色体（YPOS）的C57BL/6J（B6）小鼠中导致性反转的常染色体和X连锁基因的数量及染色体定位。B6 XYPOS小鼠要么发育为仅有卵巢组织的雌性，要么发育为具有卵巢和睾丸组织的真两性畸形个体。相比之下，YPOS染色体在大多数其他近交系背景下具有完全的雄性化作用。B6-YPOS性反转似乎是由于YPOS染色体上携带的Sry（性别决定区域，Y染色体）等位基因与源自B6的常染色体或X连锁基因座不兼容所致。我们发现有强有力的证据表明，一个名为tda1（睾丸决定，常染色体1）的基因位于第4号染色体（Chr）远端，另一个基因tda2位于Chr 2的中央区域。第5号染色体上的第三个基因tda3也有牵连，但此处证据不那么确凿。我们认为这些基因座上的B6等位基因使XYPOS胎儿易于发育卵巢组织，但没有单个基因座或基因座组合是导致性反转所必需且充分的。TDA蛋白可能调节Sry表达或与SRY蛋白形成复合物以调节其他基因，或者tda基因可能被SRY蛋白激活或抑制。
