# Cystinuria in an Australian Cattle Dog Family—A Seemingly Androgen-Associated Autosomal Dominant Trait

## TL;DR

A study finds that cystinuria in male Australian Cattle Dogs is linked to androgen hormones and may be reduced by castration.

## Contribution

The study identifies an androgen association with cystinuria in male dogs heterozygous for the SLC3A1 mutation.

## Key findings

- Castration reduced cystinuria in male dogs heterozygous for the SLC3A1 mutation.
- Heterozygous females did not show increased cystine excretion.
- The trait may be androgen-associated or involve another cystinuria type.

## Abstract

Amino acid transporter defects in the kidney can lead to cystinuria. As cystine is poorly soluble, excessive urinary excretion can lead to the formation of cystine crystals and calculi. In Australian Cattle Dogs (AUCDs), a mutation in the SLC3A1 gene was described to cause an autosomal dominant trait (cystinuria type II-A). Here we report on a family of AUCDs, where in cystinuric males heterozygous for the known mutation cystinuria decreased markedly with castration. This suggests that cystinuria and cystine calculi formation in males heterozygous for the SLC3A1 gene mutation are androgen-associated.

In Australian Cattle Dogs (AUCDs), cystinuria was reported to be an autosomal dominant trait caused by a 6 bp deletion in the SLC3A1 gene (type II-A). Here we report an androgen association in this breed. A family of 11 adult AUCDs (five intact and one neutered male and five females) was genotyped for the SLC3A1 c.1095_1100del variant, and urine was examined for concentrations of cystine, ornithine, lysine, and arginine (COLA). Among this family, three males and five females tested heterozygous for the mutation, while all other AUCDs were homozygous for the wild-type allele. The two heterozygous intact males had severe COLA-uria, which decreased markedly after castration. Neither the third heterozygous male with a history of cystine calculi but already castrated nor the five heterozygous females exhibited increased COLA-uria. Heterozygosity for the 6 bp deletion in the SLC3A1 gene was associated with cystinuria in intact male AUCDs, but not in females. Castration of the heterozygous males reduced the cystinuria. Either the type II-A cystinuria in the AUCDs is an androgen-associated dominant trait, or this family also has another type III (androgen-dependent) cystinuria. Larger surveys are needed to further define the type(s) of cystinuria and effects of castration in AUCDs.