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Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XYPOS mice
Authors:Yuria UMEMURA  Ryosuke MIYAMOTO  Rie HASHIMOTO  Kyoko KINOSHITA  Takuya OMOTEHARA  Daichi NAGAHARA  Tetsushi HIRANO  Naoto KUBOTA  Kiichi MINAMI  Shogo YANAI  Natsumi MASUDA  Hideto YUASA  Youhei MANTANI  Eiko MATSUO  Toshifumi YOKOYAMA  Hiroshi KITAGAWA  Nobuhiko HOSHI
Abstract:Mammalian sexual fate is determined by the presence or absence of sex determining region of the Y chromosome (Sry) in the “bipotential” gonads. Recent studies have demonstrated that both male and female sexual development are induced by distinct and active genetic pathways. Breeding the Y chromosome from Mus m. domesticus poschiavinus (POS) strains into C57BL/6J (B6J) mice (B6J-XYPOS) has been shown to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However, our B6N-XYPOS mice, which were generated by backcrossing of B6J-XYPOS on an inbred B6N-XX, develop as males (36%: bilateral testis with fertility as well as bilateral ovary (34%), and the remainder develop as true hermaphrodites. Here, we investigated in detail the expressions of essential sex-related genes and histological features in B6N-XYPOS mice from the fetal period to adulthood. The onsets of both Sry and SRY-box 9 (Sox9) expressions as determined spatiotemporally by whole-mount immunohistochemistry in the B6N-XYPOS gonads occurred 2–3 tail somites later than those in B6N-XYB6 gonads, but earlier than those in B6J-XYPOS, respectively. It is possible that such a small difference in timing of the Sry expression underlies testicular development in our B6N-XYPOS. Our study is the first to histologically show the expression and ectopic localization of a female-related gene in the XYPOS testes and a male-related gene in the XYPOS ovaries. The results from these and previous experiments indicate that the interplay between genome variants, epigenetics and developmental gene regulation is crucial for testis development.
Keywords:C57BL/6  Mus m  musculus poschiavinus  sex reversal  Sox9  Sry
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