title: 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.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chieh-Ying
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan Laboratory Animal Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ming-Chu
authors.initials: MC
authors.lastname: Tang
authors.affiliation: Laboratory Animal Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Kenryo
authors.initials: K
authors.lastname: Furushima
authors.affiliation: Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Chuan-Wei
authors.initials: CW
authors.lastname: Jang
authors.affiliation: Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Behringer
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan Laboratory Animal Center, National Yang-Ming University, Taipei, Taiwan cmchen@ym.edu.tw.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004251:DNA Transposable Elements; D005298:Fertility / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D008297:Male; D016296:Mutagenesis; D010902:Pituitary Gland / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D012708:Sertoli Cells / Q000378:metabolism; D013081:Sperm Motility / Q000235:genetics; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D014157:Transcription Factors
keywords: HBP2; HMG box-containing protein 2; pituitary; spermiogenesis; testis