RGD Reference Report - Genes unlinked to the leptin receptor influence urinary albumin excretion in obese Zucker rats. - Rat Genome Database

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Genes unlinked to the leptin receptor influence urinary albumin excretion in obese Zucker rats.

Authors: Kim, K  Warden, CH  Griffey, SM  Vilches-Moure, JG  Hansen, S  Cuppen, E  Nijman, IJ  Chiu, S  Stern, JS 
Citation: Kim K, etal., Physiol Genomics. 2010 Feb 16.
RGD ID: 7365117
Pubmed: (View Article at PubMed) PMID:20159938
DOI: Full-text: DOI:10.1152/physiolgenomics.90367.2008

We have previously shown that 90% of outbred obese Zucker Lepr(fa/fa) rats die prematurely of renal disease. Thus, renal disease in obese Zucker Lepr(fa/fa) rats may be caused by the LEPR mutation on chromosome 5, by the obesity, or it may be influenced by Zucker susceptibility alleles of genes on other chromosomes. We have searched for susceptibility genes on other chromosomes using urinary albumin excretion (UAE) as an early indicator of altered renal function in a backcross of (Brown Norway x inbred Zucker) F1 x inbred Zucker, which we name the BZZ cross. 237 BZZ backcross animals were sacrificed at 15 weeks of age. All included animals were homozygous for the fatty mutation of LEPR and were obese. Urinary creatinine measurements were used to calculate the Albumin to Creatinine Ratio (ACR). We identified direct effect quantitative trait loci (QTLs) for UAE and ACR on Chromosome 1 (LOD scores = 3.6 and 2.86, respectively) in males, and Chromosome 4 (LOD score = 2.9) in females. Significant QTLs were identified for left kidney weight for females on Chromosomes 3 and 12. We also demonstrated that kidneys from 15 week old obese inbred Zucker rats already show evidence of kidney pathology: tubular dilation, proteinaceous fluid accumulation, evidence for inflammation, and mild mesangial and tubular membrane basement membrane thickening. Both lean Zucker rats and the BN rats showed no evidence for these changes. Thus, by removing the influence of the Lepr(fa/fa) mutation from analysis we have identified UAE QTLs unlinked to LEPR. Key words: urinary albumin excretion, Zucker, kidney, UAE.

Annotation

Disease Annotations    
Albuminuria  (IAGP)
obesity  (IAGP,ISO)
proteinuria  (IAGP,ISO)

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Lepr  (leptin receptor)
Leprfa  (leptin receptor; fa mutant)

Genes (Mus musculus)
Lepr  (leptin receptor)

Genes (Homo sapiens)
LEPR  (leptin receptor)

QTLs
Bw124  (Body weight QTL 124)
Bw125  (Body weight QTL 125)
Kidm42  (Kidney mass QTL 42)
Stl32  (Serum triglyceride level QTL 32)
Uae40  (Urinary albumin excretion QTL 40)
Uae41  (Urinary albumin excretion QTL 41)
Uae42  (Urinary albumin excretion QTL 42)
Uae43  (Urinary albumin excretion QTL 43)
Uae44  (Urinary albumin excretion QTL 44)
Uae45  (Urinary albumin excretion QTL 45)
Uae46  (Urinary albumin excretion QTL 46)

Strains
ZUC-LeprfaSte-/-  (NA)

Objects referenced in this article
Marker rs8168428 rs8168428 Rattus norvegicus
Marker rs8165230 rs8165230 Rattus norvegicus
Marker rs105610447 rs105610447 Rattus norvegicus
Marker rs8156450 rs8156450 Rattus norvegicus
Marker rs8153618 rs8153618 Rattus norvegicus
Marker rs8158000 rs8158000 Rattus norvegicus
Marker rs8164304 rs8164304 Rattus norvegicus
Marker rs8160961 rs8160961 Rattus norvegicus
Marker rs8152181 rs8152181 Rattus norvegicus
Marker rs8163932 rs8163932 Rattus norvegicus

Additional Information