Abstract
IQ motif-containing proteins can be recognized by calmodulin (CaM) and are essential for many biological processes. However, the role of IQ motif-containing proteins in spermatogenesis is largely unknown. In this study, we identified a loss-of-function mutation in the novel gene IQ motif-containing H (IQCH) in a Chinese family with male infertility characterized by a cracked flagellar axoneme and abnormal mitochondrial structure. To verify the function of IQCH, Iqch-knockout mice were generated via CRISPR-Cas9 technology, which reproduced human phenotypes. Mechanistically, IQCH can bind to CaM and subsequently regulate the expression of RNA-binding proteins (especially HNRPAB), which are indispensable for spermatogenesis. Overall, this study revealed the function of IQCH, expanded the role of IQ motif-containing proteins in reproductive processes, and provided important guidance for genetic counseling and genetic diagnosis of male infertility.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
According to the comments of reviewers, we have refined our manuscript through professional editing services and have added method details of LC-MS/MS experiment in revised manuscript. We also have provided additional background information regarding IQ-containing protein family members and CaM, and have supplemented the data regarding mouse fertility tests and epididymal weight in revised manuscript. Furthermore, we have added quantified data about Western blotting results from Figure 6 in Figure 6-figure supplement 2. Moreover, we have included immunofluorescence images of anti-PLCz, anti-PNA and anti-IQCH and CaM during spermatogenesis development.
