PiggyBac Transposon-Mediated Mutagenesis in Rats Reveals a Crucial Role ofBbxin Growth and Male Fertility1

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Abstract

Bobby sox homolog (Bbx) is an evolutionally conserved gene, but its biological function remains elusive. Here, we characterized defects ofBbxmutant rats that were created by PiggyBac-mediated insertional mutagenesis. Smaller body size and male infertility were the two major phenotypes of homozygousBbxmutants.Bbxexpression profile analysis showed thatBbxwas more highly expressed in the testis and pituitary gland than in other organs. Histology and hormonal gene expression analysis of control andBbx-null pituitary glands showed that loss ofBbxappeared to be dispensable for pituitary histogenesis and the expression of major hormones. BBX was localized in the nuclei of postmeiotic spermatids and Sertoli cells in wild-type testes, but absent in mutant testes. An increased presence of aberrant multinuclear giant cells and apoptotic cells was observed in mutant seminiferous tubules. TUNEL-positive cells costained with CREM (round spermatid marker), but not PLZF (spermatogonia marker), gammaH2Ax (meiotic spermatocyte marker), or GATA4 (Sertoli cell marker). Finally, there were drastically reduced numbers and motility of epididymal sperm fromBbx-null rats. These results suggest that loss of BBX induces apoptosis of postmeiotic spermatids and results in spermiogenesis defects and infertility.

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