Volume 16, Issue 1 (January 2014) 16, 124–130; 10.4103/1008-682X.122592
Testis-specific Fank1 gene in knockdown mice produces oligospermia via apoptosis.
Wan-Wei Dong1, Hua-Liang Huang2, Wei Yang1, Jia Liu1, Yang Yu1, Sheng-Lai Zhou1, Wei Wang1, Xiang-Chuan Lv1, Zhao-Yang Li1, Mei-Ying Zhang1, Zhi-Hong Zheng3, Wei Yan4
1. Laboratory Animal Centre, China Medical University, Shenyang 110001, China; 2. Department of Clinical Laboratory, the Third Affiliated Hospital of Inner Mongonia Medical University, Baogang Hospital, Baotou 014010, China 3. Department of Pathology and Pathophysiology Research, China Medical University, Shenyang 110001, China; 4. Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Correspondence: Dr. ZH Zheng
Received: 08-06-2013; Revised: 25-07-2013; Accepted: 19-09-2013
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 identifi ed using cyclic amplifi cation 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.
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