title: Testis-specific Fank1 gene in knockdown mice produces oligospermia via apoptosis.
abstract: Fank1 is exclusively expressed in the testis from the meiosis phase to the haploid phase of spermatogenesis. In this study, we examined the function of Fank1 by establishing a Fank1-knockdown transgenic mouse model. The apoptotic statuses of the testes of the transgenic mice were tested using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. The FANK1 consensus DNA-binding sequence was identified using cyclic amplification of sequence target (CAST) analysis. Differentially expressed genes were examined using microarray analysis. A reduction in sperm number and an increase in apoptotic spermatocytes were observed in Fank1-knockdown mice, and the apoptotic cells were found to be primarily spermatogonia and spermatocytes. The CAST results demonstrated that the consensus DNA-binding sequence was AAAAAG, in which the percentage occurrence of each base at each position ranged from 55 to 86%. This sequence was present in the promoter regions of 10 differentially expressed genes that were examined using microarray analysis. In total, 17 genes were differentially expressed with changes in their expression levels greater than twofold. The abnormal expression of Fank1 target genes that were regulated directly or indirectly by Fank1 reduced the number of sperm in the knockdown mice. Thus, FANK1 may play a pivotal role in spermatogenesis as a transcription factor.
authors.forename: Wan-Wei
authors.initials: WW
authors.lastname: Dong
authors.forename: Hua-Liang
authors.initials: HL
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Sheng-Lai
authors.initials: SL
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiang-Chuan
authors.initials: XC
authors.lastname: Lv
authors.forename: Zhao-Yang
authors.initials: ZY
authors.lastname: Li
authors.forename: Mei-Ying
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: Laboratory Animal Centre; Department of Pathology and Pathophysiology Research, China Medical University, Shenyang, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
mesh_terms: D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009845:Oligospermia / Q000209:etiology* / Q000473:pathology; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C524049:Fank1 protein, mouse; D014157:Transcription Factors