RGD Reference Report - High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass. - Rat Genome Database

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High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass.

Authors: Nie, Y  Kumarasamy, S  Waghulde, H  Cheng, X  Mell, B  Czernik, PJ  Lecka-Czernik, B  Joe, B 
Citation: Nie Y, etal., Physiol Genomics. 2016 Jun;48(6):409-19. doi: 10.1152/physiolgenomics.00004.2016. Epub 2016 Apr 25.
RGD ID: 11353859
Pubmed: PMID:27113531   (View Abstract at PubMed)
PMCID: PMC4891933   (View Article at PubMed Central)
DOI: DOI:10.1152/physiolgenomics.00004.2016   (Journal Full-text)

Through linkage analysis of the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), a blood pressure (BP) quantitative trait locus (QTL) was previously located on rat chromosome 9. Subsequent substitution mapping studies of this QTL revealed multiple BP QTLs within the originally identified logarithm of odds plot by linkage analysis. The focus of this study was on a 14.39 Mb region, the distal portion of which remained unmapped in our previous studies. High-resolution substitution mapping for a BP QTL in the setting of a high-salt diet indicated that an SHR-derived congenic segment of 787.9 kb containing the gene secreted phosphoprotein-2 (Spp2) lowered BP and urinary protein excretion. A nonsynonymous G/T polymorphism in the Spp2 gene was detected between the S and S.SHR congenic rats. A survey of 45 strains showed that the T allele was rare, being detected only in some substrains of SHR and WKY. Protein modeling prediction through SWISSPROT indicated that the predicted protein product of this variant was significantly altered. Importantly, in addition to improved cardiovascular and renal function, high salt-fed congenic animals carrying the SHR T variant of Spp2 had significantly lower bone mass and altered bone microarchitecture. Total bone volume and volume of trabecular bone, cortical thickness, and degree of mineralization of cortical bone were all significantly reduced in congenic rats. Our study points to opposing effects of a congenic segment containing the prioritized candidate gene Spp2 on BP and bone mass.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bp392Rathypertension  IAGP  RGD 
Bp393Rathypertension  IAGP  RGD 
Bp394Rathypertension  IAGP  RGD 
Bmd92Ratosteoporosis  IAGP  RGD 
Pur33Ratproteinuria  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bmd92Ratabnormal tibia morphology  IAGP  RGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased bone volume  IAGP  RGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased compact bone area  IAGP  RGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased compact bone mass  IAGP  RGD 
SS.SHR-(D9Mco110-D9Mco124)/BjRatdecreased heart rate  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco121)/BjRatdecreased mean systemic arterial blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco124)/BjRatdecreased mean systemic arterial blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased mean systemic arterial blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco124)/BjRatdecreased pulse pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco121)/BjRatdecreased systemic arterial diastolic blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco124)/BjRatdecreased systemic arterial diastolic blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased systemic arterial diastolic blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Got111)/BjRatdecreased systemic arterial systolic blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco121)/BjRatdecreased systemic arterial systolic blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco124)/BjRatdecreased systemic arterial systolic blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased systemic arterial systolic blood pressure  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased trabecular bone connectivity density  IAGP  RGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased trabecular bone mass  IAGP  RGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased trabecular bone thickness  IAGP  RGD 
SS.SHR-(D9Mco110-D9Got111)/BjRatdecreased urine major urinary protein level  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco121)/BjRatdecreased urine major urinary protein level  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco110-D9Mco124)/BjRatdecreased urine major urinary protein level  IAGP as compared to SS/JrRGD 
SS.SHR-(D9Mco113-D9Mco124)/BjRatdecreased urine major urinary protein level  IAGP as compared to SS/JrRGD 
Bp392Ratincreased systemic arterial systolic blood pressure  IAGP  RGD 
Bp393Ratincreased systemic arterial systolic blood pressure  IAGP  RGD 
Bp394Ratincreased systemic arterial systolic blood pressure  IAGP  RGD 
Pur33Ratincreased urine protein level  IAGP  RGD 

Objects Annotated

QTLs
Bmd92  (Bone mineral density QTL 92)
Bp392  (Blood pressure QTL 392)
Bp393  (Blood pressure QTL 393)
Bp394  (Blood pressure QTL 394)
Pur33  (Proteinuria QTL 33)

Objects referenced in this article
Marker D9Mco113 D9Mco113 Rattus norvegicus
Marker D9Mco116 D9Mco116 Rattus norvegicus
Marker D9Mco124 D9Mco124 Rattus norvegicus
Marker RNO9 (SDPR-Exon 2) RNO9 (SDPR-Exon 2) Rattus norvegicus
Marker D9Mco110 D9Mco110 Rattus norvegicus
Marker D9Mco121 D9Mco121 Rattus norvegicus
Marker D9Mco114 D9Mco114 Rattus norvegicus
Marker D9Mco115 D9Mco115 Rattus norvegicus
Strain SS.SHR-(D9Mco110-D9Mco114)/Bj null Rattus norvegicus
Strain SS.SHR-(D9Mco115-D9Mco124)/Bj null Rattus norvegicus

Additional Information