Impairment of novelty detection in mice targeted for the Chl1 gene.
A deficit in cell adhesion molecules including the human Chl1 (close homologue of the L1 cell adhesion molecule) gene may cause impairment of cognitive processes. Aberrant connectivity in the CA3 region of the hippocampus has been reported in mice lacking the CHL1 protein after Chl1 gene targeting. Previous studies have observed a deficit in the processing of novel information by CHL1-deficient mice. We investigated deficits in spatial discrimination and object discrimination in three groups of mice--Chl1(+/+), Chl1(+/-) and Chl1(-/-)--performing spatial and object novelty tasks. The results indicated that wild-type mice easily recognized objects that were either "displaced" or "substituted". Chl1(-/-) mice showed severe impairment of the capacity to react to both spatial and non-spatial novelty. Chl1(+/-) mice were severely restricted in their ability to detect spatial changes, but succeeded in novel object discrimination. A dose-dependent sensitivity of the organization of the CA3 layer to the CHL1 protein may explain this result. However, the observations suggest that a dysfunction of parts of the brain other than the hippocampus may be involved in the impairment.
Pratte
Michel
M
GFCP-Inserm U910, Faculté de Médecine de la Timone, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France. michel.pratte@univmed.fr
Jamon
Marc
M
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000378:metabolism*; D004192:Discrimination, Psychological / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000235:genetics; D007859:Learning Disabilities / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013037:Spatial Behavior / Q000502:physiology*; D013997:Time Factors
D015815:Cell Adhesion Molecules; C490649:Chl1 protein, mouse