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Characterization of Nap5 KO rat for blood pressure and associated phenotypes
Author(s) -
Quinn Carol Patricia Moreno,
Mattson David L,
Geurts Aron M,
Dwinell Melinda,
Lazar Jozef,
Schilling Rebecca,
Hoffman Matthew,
Skelton Meredith,
Roman Richard J,
Cowley Allen W.,
jacob Howard J.
Publication year - 2011
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.25.1_supplement.661.15
Subject(s) - blood pressure , medicine , endocrinology , excretion , gene , phenotype , albumin , wild type , locus (genetics) , biology , renal function , creatinine , zinc finger , genetics , mutant , transcription factor
We have narrowed a locus for blood pressure to a 1.5 Mb segment on chromosome 13, which contains 16 known and predicted genes. Sequencing and expression studies have pointed out to Nap5 (Nck‐associtated protein 5) as the most likely candidate gene within the region that confers protection from the development of salt‐sensitive hypertension. Nap5 has not been related previously with blood pressure regulation. We used zinc‐finger nucleases (ZFNs) designed to target Nap5 gene in the SS rat and measured blood pressure and protein excretion in response to a high‐salt diet. Blood pressure was not different between the Nap5 −/− rats and heterozygous or wild type littermates during normal (1% NaCl) salt diet. After 7 days on high salt (8%NaCl), blood pressure was ~30 mmHg higher in the Nap5 −/− and −/+ than in the wild type controls. Plasma creatinine didn't differ between groups but protein and albumin excretion was significantly higher in the homozygous KO, both during normal and high‐salt diet, than in the wild type or heterozygous littermates. Preliminary phenotyping of Nap5 KO rats in the SS background suggests that this gene could participate in blood pressure regulation and in renal pathology or function. The exact mechanisms and pathways by which this gene has cardiovascular and renal effects needs to be further elucidated. Study funded by NIH grant HL‐82798