Item request has been placed!
×
Item request cannot be made.
×
Processing Request
Digenic Inheritance in Cystinuria Mouse Model.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Additional Information
- Source:
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
- Publication Information:
Original Publication: San Francisco, CA : Public Library of Science
- Subject Terms:
- Abstract:
Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months) and late stage (8-months) of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/-) present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/-) and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients.
- References:
Mol Biol Cell. 1999 Dec;10(12):4135-47. (PMID: 10588648)
Pediatr Nephrol. 2014 Jan;29(1):155-9. (PMID: 24045899)
Am J Physiol Renal Physiol. 2002 Sep;283(3):F540-8. (PMID: 12167606)
J Am Soc Nephrol. 2002 Oct;13(10):2547-53. (PMID: 12239244)
Hum Mol Genet. 2003 Sep 1;12(17):2097-108. (PMID: 12915471)
Hum Mol Genet. 2003 Sep 1;12(17):2109-20. (PMID: 12923163)
N Engl J Med. 1965 Dec 2;273(23):1239-45. (PMID: 5841926)
Biochim Biophys Acta. 1992 Jan 10;1103(1):101-8. (PMID: 1730012)
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9667-71. (PMID: 7568194)
J Biol Chem. 1996 Jul 26;271(30):17761-70. (PMID: 8663357)
Nat Genet. 1999 Sep;23(1):52-7. (PMID: 10471498)
Science. 1964 Jan 31;143(3605):482-4. (PMID: 14080318)
J Med Genet. 2005 Jan;42(1):58-68. (PMID: 15635077)
Nat Protoc. 2007;2(6):1356-9. (PMID: 17545973)
Nat Rev Nephrol. 2010 Jul;6(7):424-34. (PMID: 20517292)
J Genet. 2011 Apr;90(1):157-9. (PMID: 21677404)
PLoS One. 2014;9(7):e102700. (PMID: 25048459)
Am J Physiol Renal Physiol. 2013 Dec 15;305(12):F1645-55. (PMID: 24107421)
Curr Opin Genet Dev. 2001 Jun;11(3):328-35. (PMID: 11377971)
- Accession Number:
0 (Amino Acid Transport Systems, Basic)
0 (Amino Acid Transport Systems, Neutral)
0 (Slc3a1 protein, mouse)
0 (Slc7a9 protein, mouse)
- Publication Date:
Date Created: 20150912 Date Completed: 20160531 Latest Revision: 20181113
- Publication Date:
20231215
- Accession Number:
PMC4567282
- Accession Number:
10.1371/journal.pone.0137277
- Accession Number:
26359869
No Comments.