Scientists at Medical and Molecular Genetics Center release new data on cystinuria therapy
2007 OCT 8 -- Researchers detail in 'Slc7a9 knockout mouse is a good cystinuria model for antilithiasic pharmacological studies,' new data in cystinuria. According to recent research published in the American Journal of Physiology - Renal Physiology, "Cystinuria is a hereditary disorder caused by a defect in the apical membrane transport system for cystine and dibasic amino acids in renal proximal tubules and intestine, resulting in recurrent urolithiasis. Mutations in SLC3A1 and SLC7A9 genes, that codify for rBAT/b(0,+)AT transporter subunits, cause type A and B cystinuria, respectively." "In humans, cystinuria treatment is based on the prevention of calculi formation and its dissolution or breakage. Persistent calculi are treated with thiols [i.e., d-penicillamine (DP) and mercaptopropionylglycine (MPG)] for cystine solubilization. We have developed a new protocol with DP to validate our Slc7a9 knockout mouse model for the study of the therapeutic effect of drugs in the treatment of cystine lithiasis. We performed a 5-wk treatment of individually caged lithiasic mutant mice with a previously tested DP dose. To appraise the evolution of lithiasis throughout the treatment a noninvasive indirect method of calculi quantification was developed: calculi mass was quantified by densitometry of X-ray images from cystinuric mice before and after treatment. Urine was collected in metabolic cage experiments to quantify amino acids in DP-treated and nontreated, nonlithiasic mutant mice. We found significant differences between DP-treated and nontreated knockout mice in calculi size and in urinary cystine excretion. Histopathological analysis showed that globally nontreated mutant mice had more severe and diffuse urinary system damage than DP-treated mice," wrote M. Font-Llitjós and colleagues, Medical and Molecular Genetics Center. The researchers concluded: "Our results validate the use of this mouse model for testing the efficacy of potential new drugs against cystinuria.'." Font-Llitjós and colleagues published their study in American Journal of Physiology - Renal Physiology (Slc7a9 knockout mouse is a good cystinuria model for antilithiasic pharmacological studies. American Journal of Physiology - Renal Physiology, 2007;293(3):F732-40). For additional information, contact M. Font-Llitjós, L'Hospitalet de Llobregat, Medical and Molecular Genetics Center, Institut d'Investigacio Biomedica de Bellvitge, Barcelona, Spain. The publisher's contact information for the American Journal of Physiology - Renal Physiology is: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA. Keywords: Spain, Barcelona, Cystinuria Therapy, Calculi, Cystinuria, Kidney, Nephrology, Pharmaceuticals, Renal Physiology. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
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