Sex Reversal in C57BL/6J XY Mice Caused by Increased Expression of Ovarian Genes and Insufficient Activation of the Testis Determining Pathway

摘要: Sex reversal can occur in XY humans with only a single functional WT1 or SF1 allele duplication of the chromosome region containing WNT4. In contrast, mice Wt1, Sf1, Wnt4 allele, that over-express from transgene, reportedly are not sex-reversed. Because genetic background plays critical role testis differentiation, particularly C57BL/6J (B6) mice, we tested hypothesis and dosage sensitive B6 mice. We found reduced Wt1 Sf1 XYB6 impaired but no ovarian tissue developed. If, however, YAKR replaced YB6 chromosome, these otherwise genetically identical developed tissue. increased amount testicular present Sf1+/− XYAKR, Wt1+/− XYPOS, XYAKR fetuses. propose Wt1B6 Sf1B6 hypomorphic alleles testis-determining pathway genes Wnt4B6 is hypermorphic an ovary-determining gene. The latter supported by finding expression four other elevated normal XX E12.5 ovaries. to sex reversal, at least part, because they carry and/or compromise differentiation promotes ovary thereby antagonizes differentiation. Addition “weak” Sry such as one on YPOS sensitized results inappropriate development conclude dosage-sensitive this dosage-sensitivity background-dependant, mouse strains described here good models for investigation human reversal.