TAF7L regulates early stages of male germ cell development in the rat

Author:

Moreno‐Irusta Ayelen12ORCID,Dominguez Esteban M.12ORCID,Iqbal Khursheed12ORCID,Zhang Xiaoyu13,Wang Ning13ORCID,Soares Michael J.1245ORCID

Affiliation:

1. Institute for Reproductive and Developmental Sciences University of Kansas Medical Center Kansas City Kansas USA

2. Department of Pathology & Laboratory Medicine University of Kansas Medical Center Kansas City Kansas USA

3. Department of Cell Biology and Physiology University of Kansas Medical Center Kansas City Kansas USA

4. Department of Obstetrics and Gynecology University of Kansas Medical Center Kansas City Kansas USA

5. Center for Perinatal Research Children's Mercy Research Institute, Children's Mercy Kansas City Missouri USA

Abstract

AbstractMale germ cell development is dependent on the orchestrated regulation of gene networks. TATA‐box binding protein associated factors (TAFs) facilitate interactions of TATA‐binding protein with the TATA element, which is known to coordinate gene transcription during organogenesis. TAF7 like (Taf7l) is situated on the X chromosome and has been implicated in testis development. We examined the biology of TAF7L in testis development using the rat. Taf7l was prominently expressed in preleptotene to leptotene spermatocytes. To study the impact of TAF7L on the testis we generated a global loss‐of‐function rat model using CRISPR/Cas9 genome editing. Exon 3 of the Taf7l gene was targeted. A founder was generated possessing a 110 bp deletion within the Taf7l locus, which resulted in a frameshift and the premature appearance of a stop codon. The mutation was effectively transmitted through the germline. Deficits in TAF7L did not adversely affect pregnancy or postnatal survival. However, the Taf7l disruption resulted in male infertility due to compromised testis development and failed sperm production. Mutant germ cells suffer meiotic arrest at late zygotene/early pachynema stages, with defects in sex body formation. This testis phenotype was more pronounced than previously described for the subfertile Taf7l null mouse. We conclude that TAF7L is essential for male germ cell development in the rat.

Funder

Lalor Foundation

Publisher

Wiley

Subject

Genetics,Molecular Biology,Biochemistry,Biotechnology

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