Overexpression of agouti protein and stress responsiveness in mice

Ruth Babette Harris, Jun Zhou, Mingxia Shi, Stephen Redmann, Randall L. Mynatt, Donna H. Ryan

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Ectopic overexpression of agouti protein, an endogenous antagonist of melanocortin receptors' linked to the β-actin promoter (BAPa) in mice, produces a phenotype of yellow coat color, Type II diabetes, obesity and increased somatic growth. Spontaneous overexpression of agouti increases stress-induced weight loss. In these experiments, other aspects of stress responsiveness were tested in 12-week-old male wild-type mice and BAPa mice. Two hours of restraint on three consecutive days produced greater increases in corticosterone and post-stress weight loss in BAPa than wild-type mice. In Experiment 2, anxiety-type behavior was measured immediately after 12 min of restraint. This mild stress did not produce many changes indicative of anxiety, but BAPa mice spent more time in the dark side of a light-dark box and less time in the open arms of an elevated plus maze than restrained wild-type mice. In a defensive withdrawal test, grooming was increased by restraint in all mice, but the duration of each event was substantially shorter in BAPa mice, possibly due to direct antagonism of the MC4-R by agouti protein. Thus, BAPa mice showed exaggerated endocrine and energetic responses to restraint stress with small differences in anxiety-type behavior compared with wild-type mice. These results are consistent with observations in other transgenic mice in which the melanocortin system is disrupted, but contrast with reports that acute blockade of central melanocortin receptors inhibits stress-induced hypophagia. Thus, the increased stress responsiveness in BAPa mice may be a developmental compensation for chronic inhibition of melanocortin receptors.

Original languageEnglish (US)
Pages (from-to)599-608
Number of pages10
JournalPhysiology and Behavior
Volume73
Issue number4
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Agouti Signaling Protein
Melanocortin Receptors
Anxiety
Weight Loss
Melanocortins
Grooming
Corticosterone
Type 2 Diabetes Mellitus
Transgenic Mice

Keywords

  • Anxiety
  • Body weight
  • Melanocortin receptors
  • Restraint stress
  • αMSH

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

Cite this

Overexpression of agouti protein and stress responsiveness in mice. / Harris, Ruth Babette; Zhou, Jun; Shi, Mingxia; Redmann, Stephen; Mynatt, Randall L.; Ryan, Donna H.

In: Physiology and Behavior, Vol. 73, No. 4, 01.01.2001, p. 599-608.

Research output: Contribution to journalArticle

Harris, Ruth Babette ; Zhou, Jun ; Shi, Mingxia ; Redmann, Stephen ; Mynatt, Randall L. ; Ryan, Donna H. / Overexpression of agouti protein and stress responsiveness in mice. In: Physiology and Behavior. 2001 ; Vol. 73, No. 4. pp. 599-608.
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