RGD Reference Report - Isolation and confirmation of a calcium excretion quantitative trait locus on chromosome 1 in genetic hypercalciuric stone-forming congenic rats. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Isolation and confirmation of a calcium excretion quantitative trait locus on chromosome 1 in genetic hypercalciuric stone-forming congenic rats.

Authors: Hoopes RR, JR  Middleton, FA  Sen, S  Hueber, PA  Reid, R  Bushinsky, DA  Scheinman, SJ 
Citation: Hoopes RR Jr, etal., J Am Soc Nephrol. 2006 May;17(5):1292-304. Epub 2006 Apr 12.
RGD ID: 1582396
Pubmed: PMID:16611718   (View Abstract at PubMed)
DOI: DOI:10.1681/ASN.2005080828   (Journal Full-text)

Hypercalciuria is the most common risk factor for kidney stones and has a substantial genetic component. The genetic hypercalciuric stone-forming (GHS) rat model displays complex changes in physiology involving intestine, bone, and kidney and overexpression of the vitamin D receptor, thereby reproducing the human phenotype of idiopathic hypercalciuria. Through quantitative trait locus (QTL) mapping of rats that were bred from GHS female rats and normocalciuric Wistar Kyoto (WKY) male rats, loci that are linked to hypercalciuria and account for a 6 to eight-fold phenotypic difference between the GHS and WKY progenitors were mapped. GHS x WKY rats were backcrossed to breed for congenic rats with the chromosome 1 QTL HC1 on a normocalciuric WKY background. Ten generations of backcrosses produced N10F1 rats, which were intercrossed to produce rats that were homozygous for GHS loci in the HC1 region between markers D1Mit2 and D1Mit32. On a high-calcium diet (1.2% calcium), significantly different levels of calcium excretion were found between male congenic (1.67 +/- 0.71 mg/24 h) and male WKY control rats (0.78 +/- 0.19 mg/24 h) and between female congenic (3.11 +/- 0.90 mg/24 h) and female WKY controls (2.11 +/- 0.50 mg/24 h); the congenics preserve the calcium excretion phenotype of the GHS parent strain. Microarray expression analyses of the congenic rats, compared with WKY rats, showed that of the top 100 most changed genes, twice as many as were statistically expected mapped to chromosome 1. Of these, there is a clear bias in gene expression change for genes in the region of the HC1. Of >1100 gene groups analyzed, one third of the 50 most differentially expressed gene groups have direct or secondary action on calcium metabolism or transport. This is the first QTL for hypercalciuria to be isolated in a congenic animal.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hc6RatKidney Calculi  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hc6Ratincreased urine calcium level  IDA  RGD 
WKY.GHS-(D1Rat32-D1Mit32)Ratincreased urine calcium level  IAGP compared to GHSRGD 
Hc6Ratnephrolithiasis  IDA  RGD 

Related Phenotype Data for this Reference

Phenominer Options:  View all phenotype data for this reference  |  Download all phenotype data for this reference

Select a value below to view phenotype data for a specific strain, measurment, or condition.

Rat Strains:
Clinical Measurements:
Experimental Conditions:
Measurement Methods:
Objects Annotated

QTLs
Hc6  (Hypercalciuria QTL 6)

Objects referenced in this article
Strain GHS null Rattus norvegicus

Additional Information