Mutation of the dyslexia-associated gene Dcdc2 impairs LTM and visuo-spatial performance in mice

Developmental reading disorder (RD) affects 510% of school aged children, with a heritability of approximately 60%. Genetic association studies have identified several candidate RD susceptibility genes, including DCDC2; however, a direct connection between the function of these genes and cognitive or learning impairments remains unclear. Variants in DCDC2, a member of the doublecortin family of genes, have been associated in humans with RD and ADHD and Dcdc2 may play a role in neuronal migration in rats. In this study, we examined the effect of Dcdc2 mutation on cognitive abilities in mice using a visual attention and visuo-spatial learning and memory task. We show that both heterozygous and homozygous mutations of Dcdc2 result in persistent visuo-spatial memory deficits, as well as visual discrimination and long-term memory deficits. These behavioral deficits occur in the absence of neuronal migration disruption in the mutant mice, and may be comorbid with an anxiety phenotype. These are the first results to suggest a direct relationship between induced mutation in Dcdc2 and changes in behavioral measures. Dcdc2 mutant mice should prove useful in future studies designed to further dissect the underlying neural mechanisms that are impaired following Dcdc2 mutation.

Title	Mutation of the dyslexia-associated gene Dcdc2 impairs LTM and visuo-spatial performance in mice
Creator	Kass, S.
	Manglani, M.
	Che, A.
	Marin, I.
	Gabel, Lisa A.
	Murphy, C.
	LoTurco, J. J.
Publisher	Genes, Brain and Behavior
Academic Department	Psychology
Division	Social Sciences
Organization	Lafayette College
Date Issued	November 2011
Date Available	2015-04-20T20:30:52Z
Type	Article
Language	English
Keyword	Hebb-Williams maze
	visual discrimination
	working memory
	reading disorder
	developmental dyslexia
	NOR task
Bibliographic Citation	Gabel, L. A., et al. (2011 Nov.) "Mutation of the dyslexia-associated gene Dcdc2 impairs LTM and visuo-spatial performance in mice." Genes, Brain and Behavior 10 (8): 868-75.
Standard Identifier	DOI 10.1111/j.1601-183X.2011.00727.x
Standard Identifier	Handle 10385/1822
Permalink	http://hdl.handle.net/10385/1822
Rights Statement	In Copyright
Rights Holders	Kass, S.
	Manglani, M.
	Che, A.
	Marin, I.
	Gabel, Lisa A.
	Murphy, C.
	LoTurco, J. J.