RGD Reference Report - Pappa2 is linked to salt-sensitive hypertension in Dahl S rats. - Rat Genome Database

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Pappa2 is linked to salt-sensitive hypertension in Dahl S rats.

Authors: Cowley AW, JR  Yang, C  Kumar, V  Lazar, J  Jacob, H  Geurts, AM  Liu, P  Dayton, A  Kurth, T  Liang, M 
Citation: Cowley AW Jr, etal., Physiol Genomics. 2016 Jan;48(1):62-72. doi: 10.1152/physiolgenomics.00097.2015. Epub 2015 Nov 3.
RGD ID: 11553579
Pubmed: PMID:26534937   (View Abstract at PubMed)
PMCID: PMC4757026   (View Article at PubMed Central)
DOI: DOI:10.1152/physiolgenomics.00097.2015   (Journal Full-text)

A 1.37 Mbp region of chromosome 13 previously identified by exclusion mapping was consistently associated with a reduction of salt-induced hypertension in the Dahl salt-sensitive (SS) rat. This region contained five genes that were introgressed from the salt-insensitive Brown Norway (BN) rat. The goal of the present study was to further narrow that region to identify the gene(s) most likely to protect from salt-induced hypertension. The studies yielded a subcongenic SS rat strain containing a 0.71 Mbp insert from BN (26-P strain) in which salt-induced hypertension was reduced by 24 mmHg. The region contained two protein-coding genes (Astn1 and Pappa2) and a microRNA (miR-488). Pappa2 mRNA in the renal cortex of the protected 26-P was 6- to 10-fold greater than in SS fed a 0.4% NaCl diet but was reduced to levels observed in SS when fed 8.0% NaCl diet for 7 days. Compared with brain nuclei (NTS, RVLM, CVLM) and the adrenal gland, Pappa2 in the renal cortex was the only gene found to be differentially expressed between SS and 26-P and that responded to changes of salt diet. Immunohistochemistry studies found Pappa2 localized in the cytosol of the epithelial cells of the cortical thick ascending limbs. In more distal segments of the renal tubules, it was observed within tubular lumens and most notably bound to the apical membranes of the intercalated cells of collecting ducts. We conclude that we have identified a variant form of Pappa2 that can protect against salt-induced hypertension in the Dahl S rat.




Biological Process

  
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Original Reference(s)
Pappa2Ratresponse to salt stress  IEP  RGD 

Cellular Component

  
Object Symbol
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Original Reference(s)
Pappa2Ratapical plasma membrane  IDA  RGD 

1 to 14 of 14 rows
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Term
Qualifier
Evidence
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Original Reference(s)
SS.BN-(D13Hmgc1041-D13Hmgc664)/McwiRatalbuminuria inducedIAGPcontrolled sodium content diet RGD 
SS.BN-(D13Hmgc1041-D13Hmgc885)/McwiRatalbuminuria inducedIAGPcontrolled sodium content diet RGD 
SS.BN-(D13Hmgc1048-D13Hmgc1050)/McwiRatdecreased heart rate inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc1048-D13Hmgc664)/McwiRatdecreased heart rate inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc885-D13Hmgc664)/McwiRatdecreased heart rate inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc1048-D13Hmgc1045)/McwiRatdecreased susceptibility to hypertension inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc1048-D13Hmgc1050)/McwiRatdecreased susceptibility to hypertension inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc1048-D13Hmgc664)/McwiRatdecreased susceptibility to hypertension inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc885-D13Hmgc664)/McwiRatdecreased susceptibility to hypertension inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc1048-D13Hmgc1045)/McwiRatdecreased urine albumin level inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc1048-D13Hmgc1050)/McwiRatdecreased urine albumin level inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc1048-D13Hmgc664)/McwiRatdecreased urine albumin level inducedIAGPcontrolled sodium content dietcompared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc1041-D13Hmgc664)/McwiRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
SS.BN-(D13Hmgc1041-D13Hmgc885)/McwiRatsalt-sensitive hypertension inducedIAGPcontrolled sodium content diet RGD 
1 to 14 of 14 rows

Strain SS.BN-(D13Hmgc1048-D13Hmgc1050)-Pappa2em4Mcwi null Rattus norvegicus
Strain SS.BN-(D13Hmgc1048-D13Hmgc1050)-Pappa2em5Mcwi null Rattus norvegicus