Iqcm Is Dispensable for Male Fertility in Mice

ABSTRACT Objective Several IQ motif genes are highly expressed in the male reproductive tract, and mutations in human homologs are linked to reproductive defects. Iqcm shares this typical domain structure and shows high expression in the mouse testis, suggesting a potential role in fertility. However, direct in vivo evidence for this was lacking. This study aimed to determine whether Iqcm is required for male fertility in mice. Methods We generated a global Iqcm knockout mouse model using CRISPR/Cas9 technology. Male reproductive function was evaluated by examining testicular development, spermatogenesis, sperm parameters (count, morphology, and motility via CASA analysis), and long‐term breeding trials. Results Iqcm −/− males exhibited normal body growth and testicular development. Detailed analyses revealed no defects in spermatogenesis or in sperm parameters, including count, morphology, and motility. Long‐term breeding tests showed that Iqcm −/− males maintained normal fertility, with litter sizes, pregnancy rates, and pup survival rates comparable to those of wild‐type controls. Conclusion Our data indicate that Iqcm is not required for male fertility in mice under normal conditions. This study provides direct in vivo evidence that high gene expression alone does not guarantee functional importance, highlighting the need for direct genetic validation.