• PMID: 21482674
• Gene Name: EPB41L2
• Condition: Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

Lack of protein 4.1G causes altered expression and localization of the cell adhesion molecule nectin-like 4 in testis and can cause male infertility

Yang S, Weng H, Chen L, Guo X, Parra M, Conboy J, Debnath G, Lambert AJ, Peters LL, Baines AJ, Mohandas N, An X.

Protein 4.1G is a member of the protein 4.1 family, which in general serves as adaptors linking transmembrane proteins to the cytoskeleton. 4.1G is thought to be widely expressed in many cells and tissues, but its function remains largely unknown. To explore the function of 4.1G in vivo, we generated 4.1G(-/-) mice and bred the mice in two backgrounds: C57BL/6 (B6) and 129/Sv (129) hybrids (B6-129) and inbred B6. Although the B6 4.1G(-/-) mice showed no obvious abnormalities, deficiency of 4.1G in B6-129 hybrids was associated with male infertility. Histological examinations of these 4.1G(-/-) mice revealed atrophy, impaired cell-cell contact and sloughing off of spermatogenic cells in seminiferous epithelium, and lack of mature spermatids in the epididymis. Ultrastructural examination revealed enlarged intercellular spaces between spermatogenic and Sertoli cells as well as the spermatid deformities. At the molecular level, 4.1G is associated with the nectin-like 4 (NECL4) adhesion molecule. Importantly, the expression of NECL4 was decreased, and the localization of NECL4 was altered in 4.1G(-/-) testis. Thus, our findings imply that 4.1G plays a role in spermatogenesis by mediating cell-cell adhesion between spermatogenic and Sertoli cells through its interaction with NECL4 on Sertoli cells. Additionally, the finding that infertility is present in B6-129 but not on the B6 background suggests the presence of a major modifier gene(s) that influences 4.1G function and is associated with male infertility. FAU - Yang, Shaomin AU - Yang S AD - Red Cell Physiology Laboratory, New York Blood Center, New York, New York 10065, USA. FAU - Weng, Haibo AU - Weng H FAU - Chen, Lixiang AU - Chen L FAU - Guo, Xinhua AU - Guo X FAU - Parra, Marilyn AU - Parra M FAU - Conboy, John AU - Conboy J FAU - Debnath, Gargi AU - Debnath G FAU - Lambert, Amy J AU - Lambert AJ FAU - Peters, Luanne L AU - Peters LL FAU - Baines, Anthony J AU - Baines AJ FAU - Mohandas, Narla AU - Mohandas N