RGD Reference Report - Congenic substitution mapping for intracellular ca(2+) in spontaneously hypertensive rats. - Rat Genome Database

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Congenic substitution mapping for intracellular ca(2+) in spontaneously hypertensive rats.

Authors: Ohno, Y  Ando, Y  Maruyama, T  Morii, T  Eguchi, T  Hirao, K  Takenaka, T  Kanno, Y  Suzuki, H  Saruta, T 
Citation: Ohno Y, etal., Am J Hypertens. 2007 Feb;20(2):172-6.
RGD ID: 1599588
Pubmed: PMID:17261463   (View Abstract at PubMed)
DOI: DOI:10.1016/j.amjhyper.2006.07.009   (Journal Full-text)

BACKGROUND: Intracellular Ca(2+) ([Ca(2+)](i)) may be a factor of importance to hypertension in spontaneously hypertensive rats (SHR). Platelet hyperactivity caused by increased [Ca(2+)](i) may contribute to atherothrombotic cardiovascular events. In a genome scan, we have recently demonstrated that a candidate quantitative trait locus (QTL) for [Ca(2+)](i) in platelets is located near the sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase (Serca) II gene locus on chromosome 12 in backcrossed rats derived from SHR and normotensive Fischer 344 rats (F344). METHODS: Congenic substitution mapping was performed for the chromosomal region including the Serca II gene locus. The segment including the Serca II gene locus was transferred from F344 onto the genetic background of the progenitor SHR. Systolic blood pressure (SBP), platelet aggregation, and ratio of heart weight to body weight (HW/BW) as well as [Ca(2+)](i) responses in platelets were compared between SHR and the congenic strain. RESULTS: Among the parental strains, thrombin-stimulated and thapsigargin-induced peak values of [Ca(2+)](i) in platelets, platelet aggregation, SBP, and HW/BW were significantly greater in SHR than in F344 and F(1) rats. The heterozygous congenic rats for the Serca II gene segment had significantly attenuated [Ca(2+)](i) responses and platelet aggregation compared with SHR. Furthermore, they demonstrated significantly lower SBP and HW/BW. CONCLUSION: Congenic substitution mapping clarified that a chromosomal segment including the Serca II gene locus was responsible for attenuated [Ca(2+)](i) responses and platelet aggregation in the heterozygous congenic rats. Therefore, this chromosomal region may contribute to the development of hypertension and cardiac hypertrophy by augmenting Ca(2+) signaling in SHR.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  IAGP 1599588 RGD 
hypertension MODEL: controlIAGP 1599588compared to SHR/Snk strainRGD 
hypertension MODEL: spontaneousIAGP 1599588compared to F344/Snk control strainRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cardiac hypertrophy  IAGP 1599588 RGD 
decreased heart weight  IAGP 1599588compared to SHR/Snk strainRGD 
decreased platelet aggregation  IAGP 1599588compared to SHR/Snk strainRGD 
decreased platelet calcium level  IAGPthrombin or thapsigargin1599588compared to SHR/Snk strainRGD 
decreased systemic arterial systolic blood pressure  IAGP 1599588compared to SHR/Snk strainRGD 
increased heart weight  IAGP 1599588compared to F344/Snk control strainRGD 
increased platelet aggregation  IAGPbuffered calcium ion solution1599588compared to F344/Snk control strainRGD 
increased platelet calcium level  IAGPbuffered calcium ion solution and thrombin or thapsigargin1599588also with thrombin alone and compared to F344/Snk control strainRGD 
increased systemic arterial systolic blood pressure  IAGP 1599588compared to F344/Snk control strainRGD 

Objects Annotated

QTLs
Calcic2  (Intracellular calcium level QTL 2)


Additional Information