Adgb-KO Mouse

Adgb, also known as androglobin, is a chimeric protein and the most recently identified member of the mammalian globin family. It contains a calpain domain and a uniquely circularly permutated globin domain. ADGB is prominently expressed in cells with motile cilia or flagella, and is strongly associated with ciliogenesis, a process crucial for many biological functions [3,5].

In male mice, Adgb knockout leads to male infertility [2,4]. The knockout mice have reduced testis weight, abnormal sperm shape, and ultrastructural defects in microtubule and mitochondrial organization. Epididymal sperm show multiple flagellar malformations and erratic acrosomal development [4]. In humans, whole-exome sequencing identified bi-allelic deleterious variants of ADGB in infertile men with severe asthenoteratozoospermia. Spermatozoa from these patients also display acrosome and flagellum malformations [2].

In conclusion, Adgb is essential for spermatogenesis and male fertility, as demonstrated by gene knockout models in mice and human genetic studies. Understanding the function of Adgb provides new insights into the genetic causes of asthenozoospermia and male infertility, which may help in the development of molecular diagnosis and personalized genetic counseling for infertile males [1,2].

References:

1. Qu, Ronggui, Zhang, Zhihua, Wu, Ling, Chen, Biaobang, Kuang, Yanping. 2023. ADGB variants cause asthenozoospermia and male infertility. In Human genetics, 142, 735-748. doi:10.1007/s00439-023-02546-0. https://pubmed.ncbi.nlm.nih.gov/36995441/

2. Gao, Yang, Liu, Liting, Tian, Shixiong, Cao, Yunxia, He, Xiaojin. 2024. Whole-exome sequencing identifies ADGB as a novel causative gene for male infertility in humans: from motility to fertilization. In Andrology, , . doi:10.1111/andr.13605. https://pubmed.ncbi.nlm.nih.gov/38385883/

3. Koay, Teng Wei, Schödel, Johannes, Hoogewijs, David. . CRISPR Activator Approaches to Study Endogenous Androglobin Gene Regulation. In Methods in molecular biology (Clifton, N.J.), 2648, 167-185. doi:10.1007/978-1-0716-3080-8_11. https://pubmed.ncbi.nlm.nih.gov/37039991/

4. Keppner, Anna, Correia, Miguel, Santambrogio, Sara, Wenger, Roland H, Hoogewijs, David. 2022. Androglobin, a chimeric mammalian globin, is required for male fertility. In eLife, 11, . doi:10.7554/eLife.72374. https://pubmed.ncbi.nlm.nih.gov/35700329/

5. Koay, Teng Wei, Osterhof, Carina, Orlando, Ilaria M C, Hankeln, Thomas, Hoogewijs, David. 2021. Androglobin gene expression patterns and FOXJ1-dependent regulation indicate its functional association with ciliogenesis. In The Journal of biological chemistry, 296, 100291. doi:10.1016/j.jbc.2021.100291. https://pubmed.ncbi.nlm.nih.gov/33453283/