Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits

Craig H Warden, Rodrigo Gularte-Mérida, Janis S. Fisler, Susan Hansen, Noreene Shibata, Anh Le, Juan F. Medrano, Judith S. Stern

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] × ZUC Lepr faSte (ZUC)} × ZUC identified a male-specific quantitative trait locus (QTL) for urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-(D1Rat42-D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb from chromosome 1 on the ZUC background. We observed threefold higher urinary albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males than in same sex and age congenic animals when both strains are also homozygous for the ZUC leptin receptor fatty mutation (Lepr faSte) (P < 0.0001). We then linkage mapped within the donor region without confounded effects from other chromosomes. Phenotypes were collected in 248 F2 male rats in a population made by crossing parents heterozygous for both the BN donor region and ZUC Lepr faSte. Significant interactions were observed between the Lepr genotype and chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR, right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR, exhibit a second peak at the distal end of the chromosome. Hydronephrosis exhibited one or two QTLs contingent on adjustment for body weight. The results now demonstrate at least two sets of coincident traits with different correlations to kidney function.

Original languageEnglish (US)
Pages (from-to)1052-1062
Number of pages11
JournalPhysiological Genomics
Volume44
Issue number21
DOIs
StatePublished - Nov 2 2012

Fingerprint

Leptin Receptors
Chromosomes, Human, Pair 1
Albumins
Kidney
Creatinine
Quantitative Trait Loci
Congenic Animals
Chromosomes
Hydronephrosis
Chromosome Mapping
Norway
Urea
Nitrogen
Alleles
Genotype
Body Weight
Urine
Phenotype
Weights and Measures
Mutation

Keywords

  • Albumin-to-creatinine ratio
  • Congenic
  • Leptin receptor
  • Quantitative trait locus
  • Zucker

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Warden, C. H., Gularte-Mérida, R., Fisler, J. S., Hansen, S., Shibata, N., Le, A., ... Stern, J. S. (2012). Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits. Physiological Genomics, 44(21), 1052-1062. https://doi.org/10.1152/physiolgenomics.00134.2011

Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits. / Warden, Craig H; Gularte-Mérida, Rodrigo; Fisler, Janis S.; Hansen, Susan; Shibata, Noreene; Le, Anh; Medrano, Juan F.; Stern, Judith S.

In: Physiological Genomics, Vol. 44, No. 21, 02.11.2012, p. 1052-1062.

Research output: Contribution to journalArticle

Warden, CH, Gularte-Mérida, R, Fisler, JS, Hansen, S, Shibata, N, Le, A, Medrano, JF & Stern, JS 2012, 'Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits', Physiological Genomics, vol. 44, no. 21, pp. 1052-1062. https://doi.org/10.1152/physiolgenomics.00134.2011
Warden, Craig H ; Gularte-Mérida, Rodrigo ; Fisler, Janis S. ; Hansen, Susan ; Shibata, Noreene ; Le, Anh ; Medrano, Juan F. ; Stern, Judith S. / Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits. In: Physiological Genomics. 2012 ; Vol. 44, No. 21. pp. 1052-1062.
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