Skip Navigation


Human Molecular Genetics Advance Access originally published online on July 15, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
12/17/2097    most recent
ddg228v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (19)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Feliubadaló, L.
Right arrow Articles by Nunes, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Feliubadaló, L.
Right arrow Articles by Nunes, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2003, Vol. 12, No. 17 2097-2108
DOI: 10.1093/hmg/ddg228
© 2003 Oxford University Press

Slc7a9-deficient mice develop cystinuria non-I and cystine urolithiasis

Lídia Feliubadaló1,2, María Lourdes Arbonés1,{dagger}, Sandra Mañas1, Josep Chillarón2, Joana Visa3, Margot Rodés4, Ferran Rousaud5, Antonio Zorzano2,3, Manuel Palacín2,3 and Virginia Nunes1,*

1Medical and Molecular Genetics Center, Institut de Recerca Oncològica, L'Hospitalet de Llobregat, 08907 Barcelona, Spain, 2Department of Biochemistry and Molecular Biology, Universitat de Barcelona, 08028 Barcelona, Spain, 3Parc Científic de Barcelona, 08028 Barcelona, Spain, 4Institut de Bioquímica Clínica, Corporació Sanitària Clínic, 08028 Barcelona, Spain and 5Servei de Nefrologia, Fundació Puigvert, 08025 Barcelona, Spain

Received March 28, 2003; Accepted July 5, 2003

Cystinuria is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids that results in urolithiasis of cystine. Cystinuria is caused by defects in the amino acid transport system b0,+ (i.e. the rBAT/b0,+AT heteromeric complex). Mutations in SLC3A1, encoding rBAT, cause cystinuria type A, characterized by a silent phenotype in heterozygotes (phenotype I). Mutations in SLC7A9, encoding b0,+AT, cause cystinuria type B, in which heterozygotes in most cases hyperexcrete cystine and dibasic amino acids (phenotype non-I). To facilitate in vivo investigation of b0,+AT in cystinuria, Slc7a9 knockout mice have been generated. Expression of b0,+AT protein is completely abolished in the kidney of Slc7a9-/- mice (‘Stones’). In contrast, Stones expressed significant amounts of rBAT protein, which is covalently linked to unidentified light subunit(s). Stones mice present a dramatic hyperexcretion of cystine and dibasic amino acids, while Slc7a9+/- mice show moderate but significant hyperexcretion of these amino acids (phenotype non-I). Forty-two per cent of Stones mice develop cystine calculi in the urinary system. Calculi develop during the first month of life and grow throughout the life span of the animals. Histopathology in kidney reveals typical changes for urolithiasis (tubular and pelvic dilatation, tubular necrosis, tubular hyaline droplets and chronic interstitial nephritis). The fact that some Stones mice, generated in a mixed genetic background, develop cystine calculi from an early age, while others do not develop them in their first year of life, suggests the involvement of modifier genes in the lithiasis phenotype. Thus, Stones provide a valid model of cystinuria which can be used in the study of genetic, pharmacological and environmental factors involved in cystine urolithiasis.

* To whom correspondence should be addressed at: Centre de Genètica Mèdica i Molecular, Institut de Recerca Oncològica, Gran Via de Les Corts Catalanes s/n km 2,7, L'Hospitalet de Llobregat, Barcelona 08907, Spain. Email: vnunes{at}iro.es

{dagger} Present address: Genes and Disease Program, Centre de Regulació Genòmica, 08003 Barcelona, Spain.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
P. Bartoccioni, M. Rius, A. Zorzano, M. Palacin, and J. Chillaron
Distinct classes of trafficking rBAT mutants cause the type I cystinuria phenotype
Hum. Mol. Genet., June 15, 2008; 17(12): 1845 - 1854.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Font-Llitjos, L. Feliubadalo, M. Espino, R. Cleries, S. Manas, I. M. Frey, S. Puertas, G. Colell, S. Palomo, J. Aranda, et al.
Slc7a9 knockout mouse is a good cystinuria model for antilithiasic pharmacological studies
Am J Physiol Renal Physiol, September 1, 2007; 293(3): F732 - F740.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Porta, S. A. Serra, M. Huch, M. A. Valverde, F. Llorens, X. Estivill, M. L. Arbones, and E. Marti
RCAN1 (DSCR1) increases neuronal susceptibility to oxidative stress: a potential pathogenic process in neurodegeneration
Hum. Mol. Genet., May 1, 2007; 16(9): 1039 - 1050.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Fernandez, M. Jimenez-Vidal, M. Calvo, A. Zorzano, F. Tebar, M. Palacin, and J. Chillaron
The Structural and Functional Units of Heteromeric Amino Acid Transporters: THE HEAVY SUBUNIT rBAT DICTATES OLIGOMERIZATION OF THE HETEROMERIC AMINO ACID TRANSPORTERS
J. Biol. Chem., September 8, 2006; 281(36): 26552 - 26561.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
L. J. Van Winkle, J. K. Tesch, A. Shah, and A. L. Campione
System B0,+ amino acid transport regulates the penetration stage of blastocyst implantation with possible long-term developmental consequences through adulthood
Hum. Reprod. Update, March 1, 2006; 12(2): 145 - 157.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
M. Palacin, V. Nunes, M. Font-Llitjos, M. Jimenez-Vidal, J. Fort, E. Gasol, M. Pineda, L. Feliubadalo, J. Chillaron, and A. Zorzano
The Genetics of Heteromeric Amino Acid Transporters
Physiology, April 1, 2005; 20(2): 112 - 124.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
T. Verri, C. Dimitri, S. Treglia, F. Storelli, S. De Micheli, L. Ulianich, P. Vito, S. Marsigliante, C. Storelli, and B. Di Jeso
Multiple pathways for cationic amino acid transport in rat thyroid epithelial cell line PC Cl3
Am J Physiol Cell Physiol, February 1, 2005; 288(2): C290 - C303.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
M Font-Llitjos, M Jimenez-Vidal, L Bisceglia, M Di Perna, L de Sanctis, F Rousaud, L Zelante, M Palacin, and V Nunes
New insights into cystinuria: 40 new mutations, genotype-phenotype correlation, and digenic inheritance causing partial phenotype
J. Med. Genet., January 1, 2005; 42(1): 58 - 68.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.