Eef2k is not required for fertility in male mice

Abstract

Background: Eukaryotic elongation factor-2 kinase (Eef2k) is a protein kinase associated with the calmodulin-induced signaling pathway and an atypical alpha-kinase family member. Eef2kmediated phosphorylation of eukaryotic translation elongation factor 2 (Eef2) can inhibit the functionality of this protein, altering protein translation. Prior work suggests Eef2k to be overexpressed in breast, pancreatic, brain, and lung cancers wherein it may control key processes associated with apoptosis, autophagy, and cell cycle progression. The functional importance of Eef2k in the testes of male mice, however, has yet to be clarified. Methods: A CRISPR/Cas9 approach was used to generate male Eef2k-knockout mice, which were evaluated for phenotypic changes in epididymal or testicular tissues through histological and immunofluorescent staining assays. In addition, TUNEL staining was conducted to assess the apoptotic death of cells in the testis. Fertility, sperm counts, and sperm motility were further assessed.Results: Male Eef2k-knockout mice were successfully generated, and exhibited normal fertility and development. No apparent differences were observed with respect to spermatogenesis, sperm counts, or germ cell apoptosis when comparing male Eef2k −/− and Eef2k +/+ mice. Conclusions: Male Eef2k-knockout mice remained fertile and were free of any evident developmental or spermatogenic abnormalities, suggesting Eef2k to be dispensable in the context of male fertility.

Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly

“…Finally, 18 candidate genes with 43 bi-allelic loss-of-function variants were retained and validated by Sanger sequencing. Among these genes, CFAP65 , CFAP47 , FSIP2 , CFAP43 and TTC21A have been reported in other study 4 , 11 , 22 , 25 , 42 . Inner dynein arm (IDA), composed of a series of protein complex, is necessary to cilia and flagella bend formation and beating 16 .…”

“…Genomic DNA was isolated from peripheral-blood samples of the subjects using a whole blood DNA purification kit (Qiagen, Hilden, Germany). At the first stage, Whole-exome sequencing (WES) was performed on MMAF-affected subjects as previously described 4 . Briefly, genomic DNA sequencing libraries were prepared with the Nextera Rapid Capture Exome sample preparation kit, targeting >214,000 coding exons and following the protocol provided by the manufacturer (Illumina).…”

“…Male infertility, which accounts for half of all infertility cases, is generally manifested by reduced sperm count (oligozoospermia and azoospermia), reduced sperm motility (asthenozoospermia), or increased percentage of abnormal sperm morphology (teratozoospermia). Combinations are common, such as “asthenoteratozoospermia” and “oligoasthenoteratozoospermia or OAT syndrome” 3 , 4 . The flagellum integrity is essential for normal sperm function and flagellum defects consistently result in male infertility 5 .…”

Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide

“…Research shows that eEF2K-KO mice can show good life characteristics and have normal cognitive behaviors (Feng et al, 2021;Ma, 2021). Recent studies suggest that eEF2K-KO mice exhibit alleviation of age-related long-term recognition memory impairment (Gosrani et al, 2020;Shen et al, 2021).…”

eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design

“…Since eEF2 is solely inhibited through phosphorylation by eEF2K and eEF2K is an atypical α-kinase, the inhibition of eEF2K by small molecule inhibitors is a readily apparent target [ 14 , 15 ]. Compound this with the fact that eEF2K knock-out (KO) mice have been demonstrated to not display serious side effects and eEF2K KO is not required for fertility in male mice, eEF2K is presented as a unique drug target [ 14 , 16 ]. eEF2K has been deemed to be of importance as a target in cancer solid tumors, cardiovascular conditions, neurodegenerative diseases (including depression), and both hypoxic and nutritional stress [ 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”