title: An animal model of type A cystinuria due to spontaneous mutation in 129S2/SvPasCrl mice.
abstract: Cystinuria is an autosomal recessive disease caused by the mutation of either SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic 129S2/SvPasCrl mouse substrain a dramatically high frequency of kidney stones that were similar to those of patients with cystinuria. Most of 129S2/SvPasCrl exhibited pathognomonic cystine crystals in urine and an aminoaciduria profile similar to that of patients with cystinuria. In addition, we observed a heterogeneous inflammatory infiltrate and cystine tubular casts in the kidney of cystinuric mice. As compared to another classical mouse strain, C57BL/6J mice, 129S2/SvPasCrl mice had an increased mortality associated with bilateral obstructive hydronephrosis. In 129S2/SvPasCrl mice, the heavy subunit rBAT of the tetrameric transporter of dibasic amino acids was absent in proximal tubules and we identified a single pathogenic mutation in a highly conserved region of the Slc3a1 gene. This novel mouse model mimicking human disease would allow us further pathophysiological studies and may be useful to analyse the crystal/tissue interactions in cystinuria.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR S 702, Paris, France; INSERM, UMR S 702, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Livrozet
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR S 702, Paris, France; INSERM, UMR S 702, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vandermeersch
authors.affiliation: Department of Physiology and Biophysics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mesnard
authors.affiliation: Biochimie, AP-HP, Hôpital Trousseau, Paris, France.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thioulouse
authors.affiliation: Institut Pasteur, Mouse Functional Genetics Unit, Paris, France; CNRS URA 2578, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Jaubert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR S 702, Paris, France; INSERM, UMR S 702, Paris, France; Néphrologie, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR S 702, Paris, France; INSERM, UMR S 702, Paris, France; Explorations Fonctionnelles Multidisciplinaires, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Haymann
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR S 702, Paris, France; INSERM, UMR S 702, Paris, France; Explorations Fonctionnelles Multidisciplinaires, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Baud
authors.affiliation: CNRS-LCMCP- Sorbonne Universités UPMC Univ Paris 06, Collège de France, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bazin
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR S 702, Paris, France; INSERM, UMR S 702, Paris, France; Explorations Fonctionnelles Multidisciplinaires, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Daudon
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR S 702, Paris, France; INSERM, UMR S 702, Paris, France; Explorations Fonctionnelles Multidisciplinaires, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Letavernier
mesh_terms: D000595:Amino Acid Sequence; D026923:Amino Acid Transport Systems, Basic / Q000737:chemistry / Q000235:genetics*; D026921:Amino Acid Transport Systems, Neutral / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D003555:Cystinuria / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007669:Kidney Calculi / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; C489858:Slc3a1 protein, mouse