LRRC46, Leucine-rich repeat containing 46, is a member of the important LRR protein family. It is involved in multiple biological processes. In the extracellular matrix (ECM) pathway, it impacts collagen formation, which is crucial for the biomechanical structure of tissues. It also plays a role in sperm flagellum biogenesis, and may be associated with pathways related to cilia function [1,2].

In gene knockout studies, Lrrc46-/-mice showed a classical myopia phenotype. The cornea and sclera became thinner with age, limbal stem cell activity decreased, and there were microstructural changes in scleral and corneal fibroblasts. RNA-seq indicated a down-regulation of the collagen synthesis-related pathway in these mice. In sperm, knockout of Lrrc46 in mice led to typical multiple morphological abnormalities of the sperm flagella (MMAF) phenotypes, including short, coiled, and irregular flagella, reduced sperm counts, impaired motility, and male infertility. Also, CCDC181 was found to interact with LRRC46 and regulate its localization within sperm flagella [1,2,3].

In conclusion, LRRC46 is essential for the formation of collagens in eye tissues, influencing the biomechanical structure of the cornea and sclera, thus having a role in high myopia. It is also crucial for sperm flagellum biogenesis, and its mutations may be associated with MMAF-related male infertility. Studies on Lrrc46 knockout mouse models have provided valuable insights into these disease-related biological processes [1,2,3].

References:

1. Jiang, Lingxi, Dai, Chao, Wei, Yao, Huang, Lulin, Shi, Yi. 2024. Identification of LRRC46 as a novel candidate gene for high myopia. In Science China. Life sciences, 67, 1941-1956. doi:10.1007/s11427-024-2583-6. https://pubmed.ncbi.nlm.nih.gov/38874710/

2. Yin, Yingying, Mu, Wenyu, Yu, Xiaochen, Huang, Tao, Liu, Hongbin. 2022. LRRC46 Accumulates at the Midpiece of Sperm Flagella and Is Essential for Spermiogenesis and Male Fertility in Mouse. In International journal of molecular sciences, 23, . doi:10.3390/ijms23158525. https://pubmed.ncbi.nlm.nih.gov/35955660/

3. Zhang, Xiang-Jun, Hou, Xiao-Ning, Zhou, Jian-Teng, Wu, Li-Min, Shi, Qing-Hua. . CCDC181 is required for sperm flagellum biogenesis and male fertility in mice. In Zoological research, 45, 1061-1072. doi:10.24272/j.issn.2095-8137.2024.075. https://pubmed.ncbi.nlm.nih.gov/39245650/

4. Lentscher, Jessica A, Colburn, Zachary T, Ortogero, Nicole, Burney, Richard O, Chow, Gregory E. 2021. An intrauterine genomic classifier reliably delineates the location of nonviable pregnancies. In Fertility and sterility, 116, 138-146. doi:10.1016/j.fertnstert.2021.02.005. https://pubmed.ncbi.nlm.nih.gov/33771330/