Iqcg is essential for sperm flagellum formation in mice.
Mammalian spermatogenesis comprises three successive phases: mitosis phase, meiosis phase, and spermiogenesis. During spermiogenesis, round spermatid undergoes dramatic morphogenesis to give rise to mature spermatozoon, including the condensation and elongation of nucleus, development of acrosome, formation of flagellum, and removal of excessive cytoplasm. Although these transformations are well defined at the morphological level, the mechanisms underlying these intricate processes are largely unknown. Here, we report that Iqcg, which was previously characterized to be involved in a chromosome translocation of human leukemia, is highly expressed in the spermatogenesis of mice and localized to the manchette in developing spermatids. Iqcg knockout causes male infertility, due to severe defects of spermiogenesis and resultant total immobility of spermatozoa. The axoneme in the Iqcg knockout sperm flagellum is disorganized and hardly any typical ("9+2") pattern of microtubule arrangement could be found in Iqcg knockout spermatids. Iqcg interacts with calmodulin in a calcium dependent manner in the testis, suggesting that Iqcg may play a role through calcium signaling. Furthermore, cilia structures in the trachea and oviduct, as well as histological appearances of other major tissues, remain unchanged in the Iqcg knockout mice, suggesting that Iqcg is specifically required for spermiogenesis in mammals. These results might also provide new insights into the genetic causes of human infertility.
State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ren-Ke
RK
Li
State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jue-Ling
JL
Tan
State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Li-Ting
LT
Chen
Department of Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Jing-Sheng
JS
Feng
Central Laboratory, Lianyungang First People's Hospital, Lianyungang, China.
Wen-Xue
WX
Liang
State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Xue-Jiang
XJ
Guo
State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ping
P
Liu
State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhu
Z
Chen
State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Jia-Hao
JH
Sha
Department of Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Yi-Fei
YF
Wang
State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sai-Juan
SJ
Chen
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D005407:Flagella / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D008297:Male; D051379:Mice; D010641:Phenotype; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology*; D013737:Testis / Q000378:metabolism / Q000502:physiology
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; C000594470:Iqcg protein, mouse; D002118:Calcium