Missense Mutation in the Ligand-Binding Domain of the Horse Androgen Receptor Gene in a Thoroughbred Family with Inherited 64,XY (SRY+) Disorder of Sex Development.

This research investigates a newly identified androgen receptor mutation that results in a sex development disorder in horses. The mutation interrupts the functioning of the receptor’s ligand-binding domain, causing total androgen insensitivity in affected horses.

Research Context and Objectives

• The study was conducted to investigate the cause of a sex development disorder (DSD), specifically 64,XY SRY+, a testicular DSD, in a family of Thoroughbred horses. Prior to this research, only a single type of androgen receptor (AR) mutation causing a DSD had been reported in horses.
• The objective was to identify and understand the new mutation and its effects. The AR is important for processing androgen hormones, so the research aimed to understand how the mutation affected this function and led to DSD.

Findings & Methodology

• The scholars identified a missense mutation at androgen receptor exon 4 (c.2042G>C). This mutation was found to explain the presence of the DSD in the studied Thoroughbred horse family.
• The mutation is believed to affect the ligand-binding domain of the AR protein, a critical part of the molecule responsible for binding to the hormone. This disruption led to complete insensitivity to androgens in 64,XY SRY+ testicular DSD horse individuals.
• During the course of the research, they also developed a PCR-RFLP technique. This allows for accurate identification of horses carrying the mutation, which can be beneficial for breeding programs and veterinary medicine. The test makes it easier to detect affected horses and might be used for prevention and management of the condition.

Conclusion

• The research identifies a mutation in the ligand-binding domain of the horse AR gene that can cause inherited 64,XY (SRY+) DSD in Thoroughbred horses. This expands knowledge on genetic disorders in horses, particularly those concerning sex development.
• The development of the PCR-RFLP technique to identify horses with the mutation allows for improved diagnosis and can contribute to future mitigation strategies regarding genetic disorders in this species.