TAF7L REGULATES EARLY STAGES OF MALE GERM CELL DEVELOPMENT

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.Taf7lwas prominently expressed in preleptotene to leptotene spermatocytes. To study the impact of TAF7L on the testis we generated a globalloss-of-functionrat model using CRISPR/Cas9genome editing. Exon 3 of theTaf7lgene was targeted. A founder was generated possessing a 110 bp deletion within theTaf7l 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, theTaf7ldisruption resulted in male infertility due to compromised testis development and failed sperm production. Mutant germ cells suffer meiotic arrest at the zygotene stage, with defects in sex body formation and meiotic sex chromosome inactivation. This testis phenotype was more pronounced than previously described for the subfertileTaf7lnull mouse. We conclude that TAF7L is essential for male germ cell development in the rat.