Does <i>Rbmy</i> have a role in sperm development in mice?

Abstract

The Y^d1 deletion in mice removes most of the multi-copy Rbmy gene cluster that is located adjacent to the centromere on the Y short arm (Yp). XY^d1 mice develop as females because Sry is inactivated, probably because it is now juxtaposed to centromeric heterochromatin. We have previously produced XY^d1Sry transgenic males and found that they have a substantially increased frequency of abnormal sperm. Staining of testis sections with a polyclonal anti-RBMY antibody appeared to show a marked decrease of RBMY protein in the spermatids of XY^d1Sry males compared to control males, which led us to suggest that this may be responsible for the increase in sperm anomalies. In the current study we sought to determine whether augmenting Rbmy expression specifically in the spermatids of XY^d1Sry males would ameliorate the sperm defects. An expressing Rbmy transgene driven by the spermatid-specific mouse protamine 1 promotor (mP1Rbmy) was therefore introduced into XY^d1Sry males. This failed to reduce the frequency of abnormal sperm. In the course of this study, a new RBMY antibody was generated that, in contrast to the original antibody, failed to detect RBMY in spermatid stages by immunostaining. The lack of RBMY was confirmed by western blotting of lysates from purified round spermatids and elongating spermatids. The implications of these results for the proposed role for RBMY in sperm development are discussed.

The testis‐specific human protein RBMY recognizes RNA through a novel mode of interaction

“…A recent study carried out with 52 different tissues and more than 10,000 genes showed that testis has the highest rate of divergence in alternative splicing events between human and mouse (Kan et al , 2005). Our findings might explain why the mRBMY seems to have a function different from that of the hRBMY (Szot et al , 2003), as both proteins might have different RNA targets. However, we cannot rule out that the natural hRBMY target sequences differ significantly from the stem–loop motifs we identified by SELEX.…”

The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease

“…Furthermore, Sly underlies the ChrY deletion mutation phenotypes in mice that exhibit a range of deficiencies in spermatogenesis depending on the extent of the deletion (Reynard et al 2009). Rbmy is also important during spermatogenesis and encodes an RNA-binding protein that regulates mRNA splicing, and loss of RBMY expression may contribute to sperm abnormalities in mice and humans (Elliott et al 2000;Szot et al 2003;Skrisovska et al 2007;Zeng et al 2008;NavarroCosta et al 2010).…”

Sex Differences in the Age of Genetics

“…To manipulate the expression of Y genes, it is possible to decrease expression by using a mouse strain that is deficient in the region of the Y chromosome containing that gene (although such mice usually lack several Y genes) and then add back an individual Y transgene inserted onto an autosome (Szot et al, 2003).…”