
CDK8와 CDK19 유전자의 결실은 사이클린 C의 고갈을 유발하고, 이로 인해 수컷 생식계의 위축과 정자형성 장애를 초래한다.


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Paralogs CDK8 and CDK19 are regulatory kinases associated with the transcriptional Mediator complex. We have for the first time generated mice with the systemic inducible Cdk8 knockout on the background of Cdk19 constitutive knockout. Cdk8/19 double knockout (DKO) males, but not single Cdk8 and Cdk19 KO, had an atrophic reproductive system and were infertile. The DKO males lacked postmeiotic spermatids and spermatocytes after meiosis I pachytene. Testosterone levels were decreased whereas the amounts of the luteinizing hormone were unchanged. Single cell RNA sequencing showed marked differences in the expression of steroidogenic genes (such as Cyp17a1, Star and Fads ) in Leydig cells concomitant with alterations in Sertoli cells and spermatocytes likely associated with impaired synthesis of steroids. Star and Fads were also downregulated in cultivated Leydig cells after DKO. The treatment of primary Leydig cells culture with a CDK8/19 inhibitor did not induce the same changes in gene expression as DKO, and prolonged treatment of mice with a CDK8/19 inhibitor did not affect the size of testes. DKO, in contrast to single knockouts or treatment with a CDK8/19 kinase inhibitor, led to depletion of cyclin C (CcnC), the binding partner of CDK8/19 that has been implicated in CDK8/19-independent functions. This suggests that the observed phenotype was likely mediated through kinase-independent activities of CDK8/19, such as CcnC stabilization.

### Competing Interest Statement

Igor B. Roninson is Founder and President and Mengqian Chen is consultant of Senex Biotechnology, Inc. Other authors declare no conflict of interest.

Knockout of cyclin dependent kinases 8 and 19 leads to depletion of cyclin C and suppresses spermatogenesis and male fertility in mice

마우스에서-사이클린-의존성-키나제-8과-19의-결실이-사이클린-c의-고갈을-유발하고-정자형성과-수컷-불임을-억제한다


마우스에서 사이클린 의존성 키나제 8과 19의 결실이 사이클린 C의 고갈을 유발하고 정자형성과 수컷 불임을 억제한다
