Generation of humanized LDHC knock‐in mice as a tool to assess human LDHC‐targeting contraceptive drugs

• DOI: 10.1111/andr.13359
• Publication Date: 2022-12-05T04:06:11Z
• Authors: Rie Iida‐Norita; Haruhiko Miyata; Yuki Kaneda; Chihiro Emori; Taichi Noda; Tatsuya Nakagawa; Martin M. Matzuk; Masahito Ikawa
• Keywords: Male; Mice, Knockout; Spermatozoa; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Contraceptive Agents; Semen; Sperm Motility; Humans; Animals

Lactate dehydrogenase C (LDHC) is specifically expressed in male germ cells and plays critical roles glycolysis. Glycolysis required to supply energy for sperm motility. Previous studies showed that Ldhc knock-out mice exhibit impaired motility.We established human LDHC knock-in (hLDHC KI) examined whether hLDHC KI can be used assess LDHC-targeting drugs.HLDHC was knocked-in the mouse (mLdhc) allele using CRISPR/Cas9 system. Mating tests, motility examinations with a computer-assisted analysis (CASA) system, vitro fertilization (IVF) were performed. Furthermore, effect of an LDH inhibitor analyzed CASA IVF.HLDHC detected at protein level spermatozoa. exhibited comparable fertility wild-type (WT) mice. When we performed IVF more specific than mLDHC, rates reduced but not WT mice.Our results reveal rescue absence mLDHC. Differences between indicate good model inhibitors preclinical contraceptive studies.