ArticleJournal of lipid research2013
Male germ cell-specific knockout of cholesterogenic cytochrome P450 lanosterol 14α-demethylase (Cyp51).
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 23 citations in OpenAlex.
- Hepatic management of toxic sterols after acute deletion of Cyp51 from cholesterol synthesis.The Journal of biological chemistry · 2026Article
- CYP51A1 in health and disease: from sterol metabolism to regulated cell death.Cell death discovery · 2025Review
- Mechanisms of pathogenicity and the quest for genetic modifiers of kidney disease in branchiootorenal syndrome.Clinical kidney journal · 2024Article
- Endogenous sterol intermediates of the mevalonate pathway regulate HMGCR degradation and SREBP-2 processing.Journal of lipid research · 2019Article
- Retinoic acid-induced CYP51 nuclear translocation promotes meiosis prophase I process and is correlated to the expression of REC8 and STAG3 in mice.Biology open · 2018Article
- Cholesterol metabolism and Cx43, Cx46, and Cx50 gap junction protein expression and localization in normal and diabetic and obese ob/ob and db/db mouse testes.American journal of physiology. Endocrinology and metabolism · 2018Article
- Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways.eLife · 2015Article
- Identification, modeling and ligand affinity of early deuterostome CYP51s, and functional characterization of recombinant zebrafish sterol 14α-demethylase.Biochimica et biophysica acta · 2014Article
- Hidden disease susceptibility and sexual dimorphism in the heterozygous knockout of Cyp51 from cholesterol synthesis.PloS one · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome P450 lanosterol 14α-demethylase (CYP51) and its products, meiosis-activating sterols (MASs), were hypothesized by previous in vitro studies to have an important role in regulating meiosis and reproduction. To test this in vivo, we generated a conditional male germ cell-specific knockout of the gene Cyp51 in the mouse. High excision efficiency of Cyp51 allele in germ cells resulted in 85-89% downregulation of Cyp51 mRNA and protein levels in germ cells. Quantitative metabolic profiling revealed significantly higher levels of CYP51 substrates lanosterol and 24,25-dihydrolanosterol and substantially diminished levels of MAS, the immediate products of CYP51. However, germ cell-specific ablation of Cyp51, leading to lack of MAS, did not affect testicular morphology, daily sperm production, or reproductive performance in males. It is plausible that due to the similar structures of cholesterol intermediates, previously proposed biological function of MAS in meiosis progression can be replaced by some other yet-unidentified functionally redundant lipid molecule(s). Our results using the germ cell-specific knockout model provide first in vivo evidence that the de novo synthesis of MAS and cholesterol in male germ cells is most likely not essential for spermatogenesis and reproduction and that MASs, originating from germ cells, do not cell-autonomously regulate spermatogenesis and fertility.
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