RGD Reference Report - Refined mapping of blood pressure quantitative trait loci using congenic strains developed from two genetically hypertensive rat models. - Rat Genome Database

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Refined mapping of blood pressure quantitative trait loci using congenic strains developed from two genetically hypertensive rat models.

Authors: Kumarasamy, S  Gopalakrishnan, K  Toland, EJ  Yerga-Woolwine, S  Farms, P  Morgan, EE  Joe, B 
Citation: Kumarasamy S, etal., Hypertens Res. 2011 Dec;34(12):1263-70. doi: 10.1038/hr.2011.116. Epub 2011 Aug 4.
RGD ID: 6903249
Pubmed: PMID:21814219   (View Abstract at PubMed)
PMCID: PMC3808166   (View Article at PubMed Central)
DOI: DOI:10.1038/hr.2011.116   (Journal Full-text)

Previously linkage and substitution mapping were conducted between the Dahl Salt-sensitive (S) rat and the Spontaneously Hypertensive Rat (SHR) to address the hypothesis that genetic contributions to blood pressure (BP) in two genetically hypertensive rat strains are different. Among the BP quantitative trait loci (QTLs) detected, two are located on chromosome 9 within large genomic segments. The goal of the current study was to develop new iterations of congenic substrains, to further resolve both of these BP QTLs on chromosome 9 as independent congenic segments. A total of 10 new congenic substrains were developed and characterized. The newly developed congenic substrains S.SHR(9)x8Ax11A and S.SHR(9)x10Ax1, with introgressed segments of 2.05 and 6.14 Mb, represented the shortest genomic segments. Both of these congenic substrains, S.SHR(9)x8Ax11A and S.SHR(9)x10Ax1 lowered BP of the S rat by 56 mm Hg (P<0.001) and 15 mm Hg (P<0.039), respectively. The BP measurements were corroborated by radiotelemetry. Urinary protein excretion was significantly lowered by SHR alleles within S.SHR(9)x10Ax1 but not by S.SHR(9)x8Ax11A. The shorter of the two congenic segments, 2.05 Mb was further characterized and found to contain a single differentially expressed protein-coding gene, Tomoregulin-2 (Tmeff2). The protein expression of Tmeff2 was higher in the S rat compared with S.SHR(9)x8Ax11A, which also had lower cardiac hypertrophy as measured by echocardiography. Tmeff2 is known to be upregulated in patients from multiple cohorts with cardiac hypertrophy. Taken together, Tmeff2 can be prioritized as a candidate gene for hypertension and associated cardiac hypertrophy in both rats and in humans.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypotension  IAGP 6903249 RGD 
proteinuria  IAGP 6903249 RGD 

Objects referenced in this article
Marker D9Mco103 D9Mco103 Rattus norvegicus
Marker D9Mco104 D9Mco104 Rattus norvegicus
Marker D9Mco105 D9Mco105 Rattus norvegicus
Marker D9Mco106 D9Mco106 Rattus norvegicus
Marker D9Mco107 D9Mco107 Rattus norvegicus
Marker D9Mco108 D9Mco108 Rattus norvegicus
Marker D9Mco109 D9Mco109 Rattus norvegicus
Marker RNO9 (SDPR-Exon 2) RNO9 (SDPR-Exon 2) Rattus norvegicus
QTL Bp333 Blood pressure QTL 333 Rattus norvegicus
QTL Bp334 Blood pressure QTL 334 Rattus norvegicus
QTL Bp392 Blood pressure QTL 392 Rattus norvegicus
QTL Bp393 Blood pressure QTL 393 Rattus norvegicus
Strain SS.SHR-(D9Mco72-D9Rat55)/Mco null Rattus norvegicus
Strain SS.SHR-(D9Mco72-D9Rat89)/Mco null Rattus norvegicus
Strain SS.SHR-(D9Rat7-D9Mco91)/Mco null Rattus norvegicus
Strain SS.SHR-(D9Rat7-D9Rat52)/Mco null Rattus norvegicus

Additional Information