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In Vivo moduation of murine polcystic kidney (PKD) pathology by a single mutated inv gene
Author(s) -
Gattone Vincent H.,
Carr Alexander J.,
Bacallao Robert L.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.478.7
Subject(s) - nephronophthisis , locus (genetics) , biology , gene , mutant , genetics , cancer research , microbiology and biotechnology , phenotype
Significant variability between progression of PKD in two affected by the same mutation suggests modifier gene influence. PKD murine modifier gene loci were associated with chromosomal locations that harbor other PKD genes. Polymorphisms of a single mutant gene for an autosomal recessive(AR) disease could influence severity of pathology caused by a different locus. Interactions between gene products causing nephronophthisis (NPHP) include inv(nphp2) with nphp3 and nphp9. The inv locus plays a role in normal ciliogenesis, critical for PKD. We hypothesized that a mutant copy of inv would be enough to alter nphp3‐induced PKD, in vivo . FVB‐inv mutant mice were crossed with CD1‐pcy(nphp3) mice and pcy cystic pathology compared between those with inv/+ or +/+ genotype. Cystic pcy/pcy renal pathology was accelerated by the presence of the inv/+ genotype. The cpk gene is also known to interact with nphp genes and a modifier loci for cpk severity is on chromosome 4 roughly where inv gene resides. Unlike the crossing results with pcy, inv does not appear to influence the severity of cpk/cpk ARPKD (neither in kidney nor biliary pathology). In vivo studies are required to assess modifying gene capability of inv and other critical PKD associated genes.