Lrrc23-KO Mouse

LRRC23, a leucine-rich repeat-containing protein, is an essential component of the radial spoke (RS) complex, especially in the RS3 head. RS are T-shaped multiprotein complexes on axonemal microtubules that couple the central pair to modulate ciliary and flagellar motility, which is crucial for processes like sperm motility [1,3]. It was previously thought to be an ortholog of RSP15, but evolutionary and structural comparison shows that LRRC34 is the RSP15 ortholog instead [1,3].

In mice, knockout of Lrrc23 led to male infertility due to RS disorganization and impaired motility in spermatozoa, while ciliary beating was not significantly affected [4]. In humans, various mutations in LRRC23 have been identified in infertile male patients with asthenozoospermia. For example, a splice site variant in infertile patients, when mimicked in a mouse model, produced a truncated LRRC23 that failed to localize to the sperm tail, causing defective sperm motility and male infertility [1,3]. Also, a homozygous nonsense mutation in an infertile AZS patient disrupted LRRC23 synthesis and RS integrity [2]. Novel compound heterozygous mutations in a non-consanguineous family with AZS suppressed LRRC23 expression in sperm flagella and led to the absence of RS3, impairing motility [5].

In conclusion, LRRC23 is key for the integrity of the RS3 head in the flagella of mammalian spermatozoa, and its deficiency can lead to male infertility due to asthenozoospermia. Studies using gene knockout mouse models have been instrumental in revealing the role of LRRC23 in sperm motility and the molecular pathogenicity underlying reduced sperm motility in infertile human males [1-5].

References:

1. Hwang, Jae Yeon, Chai, Pengxin, Nawaz, Shoaib, Zhang, Kai, Chung, Jean-Ju. 2023. LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility. In eLife, 12, . doi:10.7554/eLife.90095. https://pubmed.ncbi.nlm.nih.gov/38091523/

2. Li, Yuqian, Zhang, Qiang, Tan, Qing, Li, Tao, Wu, Huan. 2023. LRRC23 deficiency causes male infertility with idiopathic asthenozoospermia by disrupting the assembly of radial spokes. In Clinical genetics, 104, 694-699. doi:10.1111/cge.14433. https://pubmed.ncbi.nlm.nih.gov/37804054/

3. Hwang, Jae Yeon, Chai, Pengxin, Nawaz, Shoaib, Zhang, Kai, Chung, Jean-Ju. 2023. LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.02.25.530050. https://pubmed.ncbi.nlm.nih.gov/36865175/

4. Zhang, Xin, Sun, Jiang, Lu, Yonggang, Ikawa, Masahito, Liu, Mingxi. 2021. LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice. In Journal of cell science, 134, . doi:10.1242/jcs.259381. https://pubmed.ncbi.nlm.nih.gov/34585727/

5. Tang, Song-Xi, Liu, Si-Yu, Xiao, Hong, Zhou, Hui-Liang, Liu, Ming-Xi. 2024. Novel mutations in LRRC23 cause asthenozoospermia in a nonconsanguineous family. In Asian journal of andrology, 26, 484-489. doi:10.4103/aja202435. https://pubmed.ncbi.nlm.nih.gov/39054792/