Modulation of Tcf7l2 Expression Alters Behavior in Mice

Daniel Savic; Margaret G Distler; Greta Sokoloff; Nancy A Shanahan; Stephanie C Dulawa; Abraham A Palmer; Marcelo A Nobrega

doi:10.1371/journal.pone.0026897

Back

Modulation of Tcf7l2 Expression Alters Behavior in Mice

Journal article

Open access

Peer reviewed

Modulation of Tcf7l2 Expression Alters Behavior in Mice

Daniel Savic, Margaret G Distler, Greta Sokoloff, Nancy A Shanahan, Stephanie C Dulawa, Abraham A Palmer and Marcelo A Nobrega

PloS one, Vol.6(10), p.e26897

10/27/2011

DOI: 10.1371/journal.pone.0026897

PMCID: PMC3203170

PMID: 22046400

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0026897View

Published (Version of record) Open Access

Abstract

The comorbidity of type 2 diabetes (T2D) with several psychiatric diseases is well established. While environmental factors may partially account for these co-occurrences, common genetic susceptibilities could also be implicated in the confluence of these diseases. In support of shared genetic burdens, TCF7L2 , the strongest genetic determinant for T2D risk in the human population, has been recently implicated in schizophrenia (SCZ) risk, suggesting that this may be one of many loci that pleiotropically influence both diseases. To investigate whether Tcf7l2 is involved in behavioral phenotypes in addition to its roles in glucose metabolism, we conducted several behavioral tests in mice with null alleles of Tcf7l2 or overexpressing Tcf7l2 . We identified a role for Tcf7l2 in anxiety-like behavior and a dose-dependent effect of Tcf7l2 alleles on fear learning. None of the mutant mice showed differences in prepulse inhibition (PPI), which is a well-established endophenotype for SCZ. These results show that Tcf7l2 alters behavior in mice. Importantly, these differences are observed prior to the onset of detectable glucose metabolism abnormalities. Whether these differences are related to human anxiety-disorders or schizophrenia remains to be determined. These animal models have the potential to elucidate the molecular basis of psychiatric comorbidities in diabetes and should therefore be studied further.

Biology

Medicine

Details

Title: Subtitle: Modulation of Tcf7l2 Expression Alters Behavior in Mice
Creators: Daniel Savic - University of Chicago
Margaret G Distler - University of Chicago
Greta Sokoloff - University of Chicago
Nancy A Shanahan - University of Chicago
Stephanie C Dulawa - University of Chicago
Abraham A Palmer - University of Chicago
Marcelo A Nobrega - University of Chicago
Resource Type: Journal article
Publication Details: PloS one, Vol.6(10), p.e26897
DOI: 10.1371/journal.pone.0026897
PMID: 22046400
PMCID: PMC3203170
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Alternative title: Tcf7l2 Alters Behavior in Mice
Language: English
Date published: 10/27/2011
Academic Unit: Psychological and Brain Sciences
Record Identifier: 9984256840802771

Metrics

13 Record Views

19 Times Cited - Web of Science