title: Behavioral assessment in mouse models of neuronal ceroid lipofuscinosis using a light-cued T-maze.
abstract: Learning impairment is a common feature of the neuronal ceroid lipofuscinoses (NCL), a family of lysosomal storage disorders associated with progressive neurodegeneration. Murine models for the neuronal ceroid lipofuscinoses include the well-characterized motor neuron degeneration (mnd/mnd) model for one variant of late infantile NCL (CLN8), and the more recently generated models for the infantile (CLN1) and juvenile (CLN3) forms of NCL. To determine whether these mouse models exhibit behavioral deficits analogous to the learning impairment characteristic of the human disorders, the performance of these animals on an associative learning task was assessed. The abilities of affected and normal control mice to associate a light stimulus with a food reward were evaluated in 14-16-week-old animals using a T-maze. Normal mice were able to reach a criterion for having learned to make the association within a mean of 9.4 trials. The CLN8 and CLN3 mice, on the other hand, required means of 26.2 and 27.5 trials, respectively, to reach the same performance criterion (p<0.05), whereas none of the CLN1 mice were able to reach the criterion within a limit of 30 trials. The poor performance of the mutant mice did not appear to result from impaired retinal function; mice of all three strains exhibited retinal electrophysiological responses to dim light flashes and displayed robust pupillary light reflexes. Associative learning deficits appear to be an early disease phenotype in the NCL mouse models that will be useful for assessing the efficacy of therapeutic interventions such as gene or stem cell therapies.
authors.affiliation: University of Missouri School of Medicine, Mason Eye Institute, One Hospital Drive, Columbia, MO 65212, USA.
authors.forename: Kristy D
authors.initials: KD
authors.lastname: Wendt
authors.forename: Bo
authors.initials: B
authors.lastname: Lei
authors.forename: Todd R
authors.initials: TR
authors.lastname: Schachtman
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Tullis
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ibe
authors.forename: Martin L
authors.initials: ML
authors.lastname: Katz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D003463:Cues; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004585:Electrooculography / Q000379:methods; D008027:Light; D018782:Maze Learning / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000172:deficiency; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000503:physiopathology*; D010775:Photic Stimulation / Q000379:methods; D011680:Pupil / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000528:radiation effects; D012018:Reflex / Q000528:radiation effects; D013869:Thiolester Hydrolases / Q000172:deficiency
chemical_list: C102229:CLN3 protein, mouse; C498493:Cln8 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase