Genetic analysis of the hypothalamic neurotensin system

Steven J. Garlow, Ericka Boone, Becky Kinkead, Charles B. Nemeroff

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

This study used B x D recombinant inbred mice to detect and localize genes that control the hypothalamic neurotensin (NT) system. Abundance of transcripts that encode NT and NT receptors 1, 2, and 3 (NTR1, NTR2, and NTR3) in total hypothalamic RNA was the quantitative trait measured. Analysis of transcript abundance data revealed associations with quantitative trait loci (QTL) for NT transcript abundance (NTta) on chromosome 1, 3, 6, 7, 8, and 9; for NTRIta on chromosome 3, 8, 12, and X; for NTR2ta on chromosome 2, 4, 9, 10, 12, 13, and 17; for NTR3ta on chromosome 1, 7, 11, and 12. NTta QTL on chromosomes 3, 7, and 8 coincide with QTL previously identified that impact NT peptide content and NTR2ta QTL on chromosome 2 and 12 coincide with genes previously associated with NTR2 receptor abundance. The NTta, NTR1ta, and NTR3ta QTL were not linked to their respective structural genes, but there is a highly significant (p < 0.001) association for NTR2ta on chromosome 12 that includes the Ntsr2 structural gene. There are areas of potential shared genetic regulation between NTta and NTR3ta on chromosome 1 and 7 and for all three receptors on proximal chromosome 12. The NTta QTL on chromosome 9 includes the dopamine D2 receptor (Drd2) gene and QTL involved in responses to dopaminergic agents (Hts), antipsychotics (Hpic1) and cocaine (Cocrb8), and ethanol (Etohc3). These results further strengthen the hypothesis that the NT system is involved in mediating the actions of antipsychotic agents and drugs of abuse.

Original languageEnglish (US)
Pages (from-to)535-543
Number of pages9
JournalNeuropsychopharmacology
Volume31
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Keywords

  • Hypothalamus
  • Messenger RNA
  • Neurotensin
  • Neurotensin receptor
  • QTL (quantitative trait loci)
  • RT-PCR

ASJC Scopus subject areas

  • Pharmacology

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