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.

The Ankyrin Repeat Domain 49 (ANKRD49) Augments Autophagy of Serum-Starved GC-1 Cells through the NF-κB Pathway

“…It is well established that programmed cell death (PCD) plays a principal role in processes of mammalian spermatogenesis [ 32 ]. Apoptosis, a type of PCD, plays a primary role during the different stages of spermatogenesis and has been widely studied [ 16 , 33 , 34 ]. However, the role of autophagy, another type of PCD which is equally important in spermatogenesis [ 35 ], still remains to be explored [ 36 , 37 ].…”

Altered expression of KLC3 may affect semen parameters

“…It is of note that previous studies have shown a significant correlation between testis specific transcripts, like phospholipase zeta, protamine 1, CAPZA3, and Fank1 with sperm concentration ( 30 , 31 ). Therefore, it is likely that low expression of testis transcript is associated with efficiency of spermatogenesis.…”

Normal spermatogenesis in Fank1 (fibronectin type 3 and ankyrin repeat domains 1) mutant mice

“…It was reported that Dusp1, Klk1b21 and Klk1b27 were overexpressed in Fank1 -knockdown mice and may be direct targets of Fank1 (Dong et al, 2014). However, in Fank1 −/− testis, a reduction of Klk1b21 and Klk1b27 mRNA was detected but no increase in Dusp1 transcripts (Fig.…”

“…The fibronectin type 3 and ankyrin repeat domains 1 gene ( Fank1 ) is an ancient, evolutionarily conserved gene present in vertebrates and expressed from the meiosis phase to the haploid phase of spermatogenesis in the testis (Zheng, Zheng & Yan, 2007). As a DNA binding protein, FANK1 recognizes the DNA sequence AAAAAG, and is implicated as a transcription factor during spermatogenesis (Dong et al, 2014). In a study of short-hairpin RNA (shRNA)-based knockdown transgenic mouse model, a reduction in sperm number and an increase in apoptotic germ cells were observed (Dong et al, 2014).…”

“…As a DNA binding protein, FANK1 recognizes the DNA sequence AAAAAG, and is implicated as a transcription factor during spermatogenesis (Dong et al, 2014). In a study of short-hairpin RNA (shRNA)-based knockdown transgenic mouse model, a reduction in sperm number and an increase in apoptotic germ cells were observed (Dong et al, 2014).…”