Ldhal6b-KO Mouse

Ldhal6b, lactate dehydrogenase A like 6B, is a testis-specific lactate dehydrogenase gene. Lactate dehydrogenases are involved in the reversible conversion between pyruvate and lactate, with lactate being a principal energy substrate for male germ cells [2].

In a Ldhal6b knockout mouse model, Ldhal6b was found to be dispensable for mouse development and spermatogenesis under normal laboratory conditions, as knockout mice showed normal development and no significant alterations in male fertility. Although LDHAL6B is localized to mitochondria and associated with germ granules, its depletion did not cause significant abnormalities in mitochondria, germ granules, or piRNA biogenesis. However, there were alterations in the abundance of proteins related to mitochondrial metabolism in sperm from Ldhal6b knockout mice [2]. Also, in a study generating KO mice for 12 testis-enriched genes including Ldhal6b, it was shown that these genes, when individually ablated, are not essential for male fertility [3]. In a proteomics study on busulfan-induced spermatogenesis disorder, LDHAL6B protein levels in mouse testes increased at 10 days after busulfan treatment, decreased from 20-60 days, and then gradually elevated from 70-80 days. The study also revealed 190 significantly down-regulated proteins including LDHAL6B in busulfan-treated mouse testes at 30 days [1].

In conclusion, Ldhal6b is not essential for spermatogenesis and male fertility in normal laboratory conditions as demonstrated by knockout mouse models. Understanding its role in spermatogenesis and how its expression is affected in conditions like busulfan-induced spermatogenesis disorder may provide insights into reproductive diseases [1,2,3].

References:

1. Hu, Ke, Zhu, Qinran, Zou, Jiaqi, Song, Chuanwang, Liang, Meng. 2024. Proteomic analysis for busulfan-induced spermatogenesis disorder. In Annals of medicine, 57, 2442534. doi:10.1080/07853890.2024.2442534. https://pubmed.ncbi.nlm.nih.gov/39697060/

2. Huang, Xueying, Wu, Zhicheng, Ren, Peng, Zhu, Hongwen, Dai, Peng. 2024. Lactate dehydrogenase a-like 6B is not essential for spermatogenesis and male fertility in mice. In Gene, 936, 149100. doi:10.1016/j.gene.2024.149100. https://pubmed.ncbi.nlm.nih.gov/39549775/

3. Oyama, Yuki, Miyata, Haruhiko, Shimada, Keisuke, Matzuk, Martin M, Ikawa, Masahito. . CRISPR/Cas9-mediated genome editing reveals 12 testis-enriched genes dispensable for male fertility in mice. In Asian journal of andrology, 24, 266-272. doi:10.4103/aja.aja_63_21. https://pubmed.ncbi.nlm.nih.gov/34290169/