BRDT

Bromodomain testis-specific protein is a is_associated_with::protein that in humans is encoded by the BRDT is_associated_with::gene. It is a member of the Bromodomain and Extra-terminal motif (BET) protein family.

The use of three different mouse models (Brdt knock-out mice, mice expressing a non-functional Brdt and mice expressing a mutated Brdt lacking its first bromodomain) showed that Brdt drives a meiotic and post-meiotic gene expression program. It also controls the genome-wide post-meiotic genome reorganization that occurs after histone hyperacetylation in elongating spermatids.

Model organisms
is_associated_with::Model organisms have been used in the study of BRDT function. A conditional is_associated_with::knockout mouse line, called Brdttm1a(EUCOMM)Wtsi was generated as part of the is_associated_with::International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on is_associated_with::mutant mice and two significant abnormalities were observed. Homozygous mutant males were sub-fertile and both sexes had a decreased number of is_associated_with::lumbar and sacral vertebrae.

Potential as target of male contraceptive medication
is_associated_with::BET inhibitors such as is_associated_with::JQ1 block the region of BRDT responsible for chromatin binding, and cause a reversible reduction of sperm production, sperm quality, and size of the testis in mice. The mechanism of action of JQ1 could be explained by considering Brdt’s functions as a driver of testis-specific gene expression and post-meiotic chromatin reorganization. As BET inhibitors also inhibit other BET proteins BRD2, BRD3, and BRD4, they are likely to have effects in people beyond temporary male sterility.