MKRN2 knockout causes male infertility through decreasing STAT1, SIX4, and TNC expression

Front Endocrinol (Lausanne). 2023 Mar 10:14:1138096. doi: 10.3389/fendo.2023.1138096. eCollection 2023.

Abstract

Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. Although recent studies have shed insights on the potential causes of male infertility, its underlining mechanisms still remain to be elucidated. We developed a Mrkn2 knockout mice model to study this gene and found that deletion of Mkrn2 in mice led to male infertility. Interestingly, the expression level of signal transducer and activator of the transcription (STAT)1 was significantly decreased in MKRN2 knockout testis and MEF cells. Co-IP assay showed an interaction between MKRN2 and STAT1. Moreover, our results further indicated that MKRN2 regulated the expression level of SIX4 and tenascin C (TNC) via the EBF transcription factor 2 (EBF2) in mice. The results of our study will provide insights into a new mechanism of male infertility.

Keywords: MKRN2; SIX4; STAT1; TNC; male infertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Homeodomain Proteins / metabolism
  • Humans
  • Infertility, Male* / genetics
  • Male
  • Mice
  • Ribonucleoproteins* / genetics
  • Ribonucleoproteins* / metabolism
  • STAT1 Transcription Factor / metabolism
  • Tenascin / metabolism
  • Trans-Activators / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Ebf2 protein, mouse
  • Homeodomain Proteins
  • Mkrn2 protein, mouse
  • Ribonucleoproteins
  • SIX4 protein, human
  • Stat1 protein, mouse
  • STAT1 Transcription Factor
  • Tenascin
  • Trans-Activators

Grants and funding

This work was supported in part by the National Natural Science Foundation of China (No. 81903174).