RGD Reference Report - Susceptibility to Hypertensive Renal Disease in the Spontaneously Hypertensive Rat Is Influenced by 2 Loci Affecting Blood Pressure and Immunoglobulin Repertoire. - Rat Genome Database

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Susceptibility to Hypertensive Renal Disease in the Spontaneously Hypertensive Rat Is Influenced by 2 Loci Affecting Blood Pressure and Immunoglobulin Repertoire.

Authors: Dhande, Isha S  Cranford, Stacy M  Zhu, Yaming  Kneedler, Sterling C  Hicks, M John  Wenderfer, Scott E  Braun, Michael C  Doris, Peter A 
Citation: Dhande IS, etal., Hypertension. 2018 Apr;71(4):700-708. doi: 10.1161/HYPERTENSIONAHA.117.10593. Epub 2018 Feb 5.
RGD ID: 14348961
Pubmed: PMID:29437896   (View Abstract at PubMed)
PMCID: PMC5843527   (View Article at PubMed Central)
DOI: DOI:10.1161/HYPERTENSIONAHA.117.10593   (Journal Full-text)

High blood pressure exerts its deleterious effects on health largely through acceleration of end-organ diseases. Among these, progressive loss of renal function is particularly important, not only for the direct consequences of kidney damage but also because loss of renal function is associated with amplification of other adverse cardiovascular outcomes. Genetic susceptibility to hypertension and associated end-organ disease is non-Mendelian in both humans and in a rodent model, the spontaneously hypertensive rat (SHR). Here, we report that hypertensive end-organ disease in the inbred SHR-A3 line is attributable to genetic variation in the immunoglobulin heavy chain on chromosome 6. This variation coexists with variation in a 10 Mb block on chromosome 17 that contains genetic variation in 2 genes involved in immunoglobulin Fc receptor signaling. Substitution of these genomic regions into the SHR-A3 genome from the closely related, but injury-resistant, SHR-B2 line normalizes both biomarker and histological measures of renal injury. Our findings indicate that genetic variation leads to a contribution by immune mechanisms hypertensive end-organ injury and that, in this rat model, disease is influenced by differences in germ line antibody repertoire.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased urine HAVCR1 level  IAGP 14348961males compared to SHRSP/BbbUtx malesRGD 
decreased urine lipocalin 2 level  IAGP 14348961males compared to SHRSP/BbbUtx malesRGD 
decreased urine osteopontin level  IAGP 14348961males compared to SHRSP/BbbUtx malesRGD 
Objects Annotated

Strains
SHR/Utx  (NA)

Objects referenced in this article
Marker rs198233821 rs198233821 Rattus norvegicus
Marker rs198932221 rs198932221 Rattus norvegicus

Additional Information