title: The development of behavioral abnormalities in the motor neuron degeneration (mnd) mouse.
abstract: The motor neuron degeneration (mnd) mouse, which has widespread abnormal accumulating lipoprotein and neuronal degeneration, has a mutation in CLN8, the gene for human progressive epilepsy with mental retardation (EPMR). EPMR is one of the neuronal ceroid lipofuscinoses (NCLs), a group of neurological disorders characterized by autofluorescent lipopigment accumulation, blindness, seizures, motor deterioration, and dementia. The human phenotype of EPMR suggests that, in addition to the motor symptoms previously categorized, various types of progressive behavioral abnormalities would be expected in mnd mice. We have therefore examined exploratory behavior, fear conditioning, and aggression in 2-3 month and 4-5 month old male mnd mice and age-matched C57BL/6 (B6) controls. The mnd mice displayed increased activity with decreased habituation in the activity monitor, poor contextual and cued memory, and heightened aggression relative to B6 controls. These behavioral deficits were most prominent at 4-5 months of age, which is prior to the onset of gross motor symptoms at 6 months. Our results provide a link from the mutation via pathology to a quantifiable multidimensional behavioral phenotype of this naturally occurring mouse model of NCL.
authors.affiliation: Wadsworth Center, New York State Department of Health, David Axelrod Institute, 120 New Scotland Avenue, P.O. Box 22002, Albany, NY 12201, USA.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Bolivar
authors.forename: J
authors.initials: J
authors.lastname: Scott Ganus
authors.forename: Anne
authors.initials: A
authors.lastname: Messer
mesh_terms: D000374:Aggression / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000473:pathology; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000235:genetics / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000235:genetics / Q000523:psychology*; D016472:Motor Neuron Disease / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D010641:Phenotype
chemical_list: C498493:Cln8 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins