Re: Cystinuria: Genetic Aspects, Mouse Models, and a New Approach to Therapy
Abstract
available at http://www.ncbi.nlm.nih.gov/pubmed/30515543 Editorial Comment: Cystinuria is a genetic disease associated with abnormal amino acid (cystine, ornithine, lysine and arginine) transport in the kidney and gut. A transporter protein complex composed of 2 subunits generated from 2 genes, SLC3A1 and SLC7A9, promotes transport of these amino acids in the renal proximal tubule. Mutations in these genes may lead to cystinuria. Murine knockout models for cystinuria have been used to assess potential therapeutic approaches. This article provides a nice in-depth review of these models, which include Slc3a1, Slc7a9 and double mutants (Slc3a1/Slc7a9). The Slc3a1 and Slc7a9 homozygote animals excrete increased amounts of cystine. The Slc7a9 heterozygotes excrete an intermediate amount of cystine, while the Slc3a1 heterozygote excretion is similar to wild-type animals. The double mutants have the highest cystine excretion. Stone formation in mice typically occurs in the bladder. Slc3a1 females have less bladder stone activity compared to males. Thus, a search for factors that drive this gender difference should be undertaken. The findings may provide insight into why phenotypic manifestations in patients with similar “cystinuria” mutations may differ. Dean G. Assimos, MD Suggested Reading Reinstatler L, Stern K, Batter H et al: Conversion from cystine to noncystine stones: incidence and associated factors. J Urol 2018; 200: 1285. Coe FL, Clark C, Parks JH et al: Solid phase…
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