QTL mapping for traits associated with stress neuroendocrine reactivity in rats.
In the present study we searched for quantitative trait loci (QTLs) that affect neuroendocrine stress responses in a 20-min restraint stress paradigm using Brown-Norway (BN) and Wistar-Kyoto-Hyperactive (WKHA) rats. These strains differed in their hypothalamic-pituitary-adrenal axis (plasma ACTH and corticosterone levels, thymus, and adrenal weights) and in their renin-angiotensin-aldosterone system reactivity (plasma renin activity, aldosterone concentration). We performed a whole-genome scan on a F2 progeny derived from a WKHA x BN intercross, which led to the identification of several QTLs linked to plasma renin activity (Sr6, Sr8, Sr11, and Sr12 on chromosomes RNO2, 3, 19, and 8, respectively), plasma aldosterone concentration (Sr7 and Sr9 on RNO2 and 5, respectively), and thymus weight (Sr10, Sr13, and Srl4 on RNO5, 10, and 16, respectively). The type 1b angiotensin II receptor gene (Agtrlb) maps within the confidence intervals of QTLs on RNO2 linked to plasma renin activity (Sr6, highly significant; LOD = 5.0) and to plasma aldosterone level (Sr7, suggestive; LOD = 2.0). In vitro studies of angiotensin II-induced release of aldosterone by adrenal glomerulosa cells revealed a lower receptor potency (log EC50 = -8.16 +/- 0.11 M) and efficiency (Emax = 453.3 +/- 25.9 pg/3 x 10(4) cells/24 h) in BN than in WKHA (log EC50 = -10.66 +/- 0.18 M; Emax = 573.1 +/- 15.3 pg/3 x 10(4) cells/24 h). Moreover, differences in Agtr1b mRNA abundance and sequence reinforce the putative role of the Agtr1b gene in the differential plasma renin stress reactivity between the two rat strains.
Llamas
Bastien
B
Laboratoire Neurogénétique et Stress, INSERM U471/INRA UMR1243, Université Victor Segalen Bordeaux 2, Institut François Magendie, Rue Camille Saint Saens, 33077 Bordeaux cedex, France.
Contesse
Vincent
V
Guyonnet-Duperat
Véronique
V
Vaudry
Hubert
H
Mormède
Pierre
P
Moisan
Marie-Pierre
MP
D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000075244:Apelin Receptors; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D005838:Genotype; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008126:Lod Score; D008297:Male; D009841:Oligonucleotides; D009929:Organ Size; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D040641:Quantitative Trait Loci; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013312:Stress, Physiological / Q000235:genetics* / Q000378:metabolism; D013950:Thymus Gland / Q000033:anatomy & histology
D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D009841:Oligonucleotides; D043562:Receptors, G-Protein-Coupled; D000450:Aldosterone; D012083:Renin