Aim: We have previously demonstrated different sensitivity between DA and WOKW rats to the central hyperphagic effect of the Nociceptin/Orphanin FQ (N/OFQ) peptide. In this study we invistigated the effect of N/OFQ in congenics DA.WOKW to elucidate the genetic basis of N/OFQ-induced hyperphagia. Material and methods: DA.WOKW rats were generated as speed-congenics by a cross of WOKW and DA rats using marker-aided selection. The resulting cross hybrids were repeatedly backcrossed with DA using animals which were heterozygous at loci D3Mgh5, D3Rat1 (DA.3Wa) or D3Mit10, D3Rat189 (DA.3Wb) or D5Mgh6, D5Mit5 (DA.5W) or D9Mgh1, D16Rat89 (DA.16W) and were most homozygous for DA alleles at 180 background loci. After 5 backcross generations, the animals were intercrossed. Animals homozygous for WOKW alleles at the loci of interest were selected and founded the congenic DA.3Wa, DA.3Wb, DA.5W and DA.16W rat strains. Founder animals were fine mapped with more than 30 polymorphic markers on chromosomes 3, 5, and 16. Six males of each congenic strain and DA as well as WOKW rats were injected into the lateral brain ventricle with N/OFQ (2.1, 4.2, 8.4 nmol/rat) and their feeding responses were measured for the following 2h. Results: DA, DA.5W, DA.3Wb significantly dose-dependently increased their food intake after N/OFQ injection. On the other hand, WOKW, and DA.16W rat did not show any significant increase in food intake. Conclusions: The exchange of a region on chromosomes 3b and 5, but not in chromosome 16 significantly produced alteration of feeding in these animals. However, these resistant WOKW and chromosome 16 congenic animals could help to identify the genetic basis of N/OFQ-induced hyperphagia.

Differential feeding responses to Nociceptin/Orphanin FQ in Dark Agouti, Wistar Ottawa Karlsburg W and congenics DA.WOKW rats

CIFANI, Carlo;MASSI, Maurizio;POLIDORI, Carlo;
2008-01-01

Abstract

Aim: We have previously demonstrated different sensitivity between DA and WOKW rats to the central hyperphagic effect of the Nociceptin/Orphanin FQ (N/OFQ) peptide. In this study we invistigated the effect of N/OFQ in congenics DA.WOKW to elucidate the genetic basis of N/OFQ-induced hyperphagia. Material and methods: DA.WOKW rats were generated as speed-congenics by a cross of WOKW and DA rats using marker-aided selection. The resulting cross hybrids were repeatedly backcrossed with DA using animals which were heterozygous at loci D3Mgh5, D3Rat1 (DA.3Wa) or D3Mit10, D3Rat189 (DA.3Wb) or D5Mgh6, D5Mit5 (DA.5W) or D9Mgh1, D16Rat89 (DA.16W) and were most homozygous for DA alleles at 180 background loci. After 5 backcross generations, the animals were intercrossed. Animals homozygous for WOKW alleles at the loci of interest were selected and founded the congenic DA.3Wa, DA.3Wb, DA.5W and DA.16W rat strains. Founder animals were fine mapped with more than 30 polymorphic markers on chromosomes 3, 5, and 16. Six males of each congenic strain and DA as well as WOKW rats were injected into the lateral brain ventricle with N/OFQ (2.1, 4.2, 8.4 nmol/rat) and their feeding responses were measured for the following 2h. Results: DA, DA.5W, DA.3Wb significantly dose-dependently increased their food intake after N/OFQ injection. On the other hand, WOKW, and DA.16W rat did not show any significant increase in food intake. Conclusions: The exchange of a region on chromosomes 3b and 5, but not in chromosome 16 significantly produced alteration of feeding in these animals. However, these resistant WOKW and chromosome 16 congenic animals could help to identify the genetic basis of N/OFQ-induced hyperphagia.
2008
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/202272
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