Androgen Insensitivity Syndrome (AIS)

Androgen insensitivity syndrome (AIS) is an inherited X-linked recessive disorder. In affected individuals, the male reproductive organs develop abnormally. The normal karyotype of mares is 64, XX, while that of stallions is 64, XY. The genetic information carried by the sex chromosomes regulates the subsequent normal development of sexual characteristics. The formation of the testes and the subsequent production of testosterone lead to masculinization of the external genitalia. Active involvement of androgens (male hormones) is required for masculinization to occur. If androgens cannot perform their function properly – either because they are completely absent or because the tissues do not respond to them – the external genitalia gradually differentiate as female. This physiological phenomenon is referred to as male pseudohermaphroditism.

Mares may have a larger body frame, increased musculature, and a prominent neck. Their behaviour resembles that of stallions. Marked vocalization in the presence of mares in oestrus, aggression towards other horses, and absence of oestrus are common. The external genitalia appear female at first glance; the vagina is shortened, the cervix is not detectable, and the uterus is absent. During abdominal ultrasound examination, two testes may be visible near the normal position of the ovaries. The presence of testes explains the normal to elevated testosterone levels.

A mutation in the AR gene (g.52728703A>G) was identified in Quarter Horses and related breeds. This was the first mutation found to be associated with a diagnosis of AIS and is therefore designated AR1. During the critical period of male embryonic development, a reduced amount of functional AR gene product is expressed, leading to subsequent abnormalities in the development of the male reproductive organs.

Resulting genotypes:

• X/X – healthy mare, does not carry the mutation in the AR gene and does not transmit it to her offspring
• X/Y – healthy stallion, not affected by AIS
• X(AR1)/X – heterozygous mare, has no symptoms but carries the mutation and has a 50% probability of transmitting it to her offspring
• X(AR1)/Y – affected stallion, external genitalia appear female, the genotype is male, the mutation is not transmitted further – the individual is infertile

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Howden, Krista J. "Androgen insensitivity syndrome in a thoroughbred mare (64, XY—testicular feminization)." The Canadian Veterinary Journal 45.6 (2004): 501.

Révay, T., et al. "GTG mutation in the start codon of the androgen receptor gene in a family of horses with 64, XY disorder of sex development." Sexual Development 6.1-3 (2012): 108-116.