Absence of Correlation betweenSryPolymorphisms and XY Sex Reversal Caused by theM. m. domesticusY Chromosome

Abstract

Mus musculus domesticusY chromosomes (YDOMChrs) vary in their ability to induce testes in the strain C57BL/6J. In severe cases, XY females develop (XYDOMsex reversal). To identify the molecular basis for the sex reversal, a 2.7-kb region ofSry,the testis-determining gene, was sequenced from YDOMChrs linked to normal testis determination, transient sex reversal, and severe sex reversal. Four mutations were identified. However, no correlation exists between these mutations and severity of XYDOMsex reversal. RT-PCR identifiedSrytranscripts in XYDOMsex-reversed fetal gonads at 11 d.p.c., the age whenSryis hypothesized to function. In addition, no correlation exists between XYDOMsex reversal and copy numbers of pSx1, a Y-repetitive sequence whose deletion is linked to XY sex reversal. We conclude that SRY protein variants, blockade ofSrytranscription, and deletion of pSx1 sequences are not the underlying causes of XYDOMsex reversal.