PiggyBac Transposon-Mediated Mutagenesis in Rats Reveals a Crucial Role of Bbx in Growth and Male Fertility

Abstract

Bobby sox homolog (Bbx) is an evolutionally conserved gene, but its biological function remains elusive. Here, we characterized defects of Bbx mutant rats that were created by PiggyBac-mediated insertional mutagenesis. Smaller body size and male infertility were the two major phenotypes of homozygous Bbx mutants. Bbx expression profile analysis showed that Bbx was more highly expressed in the testis and pituitary gland than in other organs. Histology and hormonal gene expression analysis of control and Bbx-null pituitary glands showed that loss of Bbx appeared 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 from Bbx-null rats. These results suggest that loss of BBX induces apoptosis of postmeiotic spermatids and results in spermiogenesis defects and infertility.

Whole-Genome Resequencing of Xiangxi Cattle Identifies Genomic Diversity and Selection Signatures

“…Among them, 127 genes were overlapped which were considered to be candidate genes ( Supplementary Table S6 ). The annotations of candidate genes revealed the functions that may be associated with economic traits, including reproduction ( KHDRBS2 , GOLGA4 , BBX , BANF2 , INSL6 ) ( Cai et al, 2017 ; Guo et al, 2018 ; Ortega et al, 2016 ; Pini et al, 2020 ; Wang et al, 2016 ), growth ( RALGAPA1 , NCK1 , VGLL2, FGFR3 ) ( Aryal et al, 2015 ; Honda et al, 2017 ; Sun et al, 2020 ; Wen et al, 2016 ), meat quality ( PLIN4 ) ( Pena et al, 2019 ), and somatotype ( SYN3 ) ( An et al, 2019 ). We also obtained genes ( ELANE, AZU1 ) ( Cui et al, 2021 ; Zhang et al, 2021 ) related to immune response, which may result from long-term natural selection.…”

Human papillomavirus and the landscape of secondary genetic alterations in oral cancers

“…BBX is a member of the high-mobility group (HMG) box-containing family of transcription factor genes that includes SOX2 and HMGB1. Model systems support its role in regulation of the G1/S cell cycle transition (Chen et al 2014b) and stem cell differentiation (Wang et al 2016). BBX is located on the frequently amplified region on Chr 3q and is coordinately overexpressed.…”

Single-Cell RNA Sequencing Defines the Regulation of Spermatogenesis by Sertoli-Cell Androgen Signaling

“…For example, Bbx is an evolutionally conserved gene and localized in the nuclei of both Sertoli cells and postmeiotic spermatids in the testis. However, loss of BBX leads to apoptosis of postmeiotic spermatids, spermiogenesis defects and ultimately, male infertility ( Wang et al, 2016 ). Results from the scRNA-seq indicate that androgens could promote Bbx expression, suggesting that inhibition may exert deleterious effects on normal testicular function.…”