GeneSet Information

Tier II GS223181 • Saline consumption QTL 1 (Salc1 Published QTL Chr 4)

DESCRIPTION:

QTL Associated with Consumption level. On Chromosome 4 with a LOD score= 11.26, p-value =. From a(n) of

LABEL:

QTL-Salc1-Rat-Chr 4

SCORE TYPE:

Binary

DATE ADDED:

2015-06-10

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Marissal-Arvy N, Lombès M, Petterson J, Moisan MP, Mormède P

TITLE:

Gain of function mutation in the mineralocorticoid receptor of the Brown Norway rat.

JOURNAL:

The Journal of biological chemistry None None, Vol 279, pp. 39232-9

ABSTRACT:

1. J Biol Chem. 2004 Sep 17;279(38):39232-9. Epub 2004 Jul 12. Gain of function mutation in the mineralocorticoid receptor of the Brown Norway rat. Marissal-Arvy N(1), Lombès M, Petterson J, Moisan MP, Mormède P. Author information: (1)Neurogénétique et Stress, Institut National de la Santé et de la Recherche Médicale, Unité 471, Université de Bordeaux 2, France. marissal@bordeaux.inserm.fr The aim of this research was to identify the molecular bases of differences in sensitivity to corticosteroid hormones between Brown Norway and Fischer 344 rats. We previously showed an apparent insensitivity to adrenalectomy in Brown Norway rats. Based on our first hypothesis of a different activity/reactivity of the mineralocorticoid signaling pathway between the two rat strains, we sequenced Brown Norway and Fischer 344 mineralocorticoid receptor cDNA and identified a tyrosine to cysteine substitution (Y73C) in the N-terminal part of the Brown Norway mineralocorticoid receptor. As a first step, this substitution gave us a means to distinguish the Brown Norway allele from the Fischer 344 at the mineralocorticoid receptor locus in an F2 population. We showed a strong genetic linkage between the mineralocorticoid receptor genotype and sensitivity to adrenalectomy. A subsequent genome-wide linkage analysis confirmed the involvement of the mineralocorticoid receptor locus and implicated other loci, including one on chromosome 4, which collectively explain a large part of the strain differences in corticosteroid receptor responses. In vitro studies further revealed that the Y73C substitution induces greater transactivation of the mineralocorticoid receptor by aldosterone, and surprisingly by progesterone as well, which could substitute for aldosterone after adrenalectomy in Brown Norway rats. We challenged this hypothesis in vivo and showed that plasma progesterone is higher in Brown Norway male rats and partially compensates for aldosterone after adrenalectomy. This work illustrates the interest of a pluristrategic approach to explore the mineralocorticoid receptor signaling pathway and its implication in the regulation of hydroelectrolytic homeostasis and blood pressure. PMID: 15252022 [PubMed - indexed for MEDLINE] PUBMED: 15252022
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