title: Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse.
abstract: Using apolipoprotein E knockout mice derived from the Maeda source [Piedrahita J. A. et al. (1992) Proc. natn. Acad Sci. US.A. 89, 4471 4475], we have studied the influence of apolipoprotein E gene deletion on normal CNS function by neurological tests and water maze learning, hippocampal ultrastructure assessed by quantitative immunocytochemistry and electron microscopy, CNS plasticity, i.e. hippocampal long-term potentiation and amygdaloid kindling, and CNS repair, i.e. synaptic recovery in the hippocampus following deafferentation. In each study there was little difference between the apolipoprotein E knockout mice and wild-type controls of similar age and genetic background. Apolipoprotein E knockout mice aged eight months demonstrated accurate spatial learning and normal neurological function. Synaptophysin and microtubule-associated protein 2 immunohistochemistry and electron microscopic analysis of these animals revealed that the hippocampal synaptic and dendritic densities were similar between genotypes. The induction and maintenance of kindled seizures and hippocampal long-term potentiation were indistinguishable between groups. Finally, unilateral entorhinal cortex lesions produced a marked loss of hippocampal synaptophysin immunoreactivity in both groups and a marked up-regulation of apolipoprotein E in the wild-type group. Both apolipoprotein E knockout and wild-type groups showed immunohistochemical evidence of reactive synaptogenesis, although the apolipoprotein E knockout group may have initially shown greater synaptic loss. It is suggested that either apolipoprotein E is of no importance in the maintenance of synaptic integrity and in processes of CNS plasticity and repair, or more likely, alternative (apolipo)proteins may compensate for the loss of apolipoprotein E in the knockout animals.
authors.affiliation: Neuroscience Unit, Glaxo Wellcome Research and Development, Medicines, Research Centre, Stevenage, Herts, UK.
authors.forename: R
authors.initials: R
authors.lastname: Anderson
authors.forename: J C
authors.initials: JC
authors.lastname: Barnes
authors.forename: T V
authors.initials: TV
authors.lastname: Bliss
authors.forename: D P
authors.initials: DP
authors.lastname: Cain
authors.forename: K
authors.initials: K
authors.lastname: Cambon
authors.forename: H A
authors.initials: HA
authors.lastname: Davies
authors.forename: M L
authors.initials: ML
authors.lastname: Errington
authors.forename: L A
authors.initials: LA
authors.lastname: Fellows
authors.forename: R A
authors.initials: RA
authors.lastname: Gray
authors.forename: T
authors.initials: T
authors.lastname: Hoh
authors.forename: M
authors.initials: M
authors.lastname: Stewart
authors.forename: C H
authors.initials: CH
authors.lastname: Large
authors.forename: G A
authors.initials: GA
authors.lastname: Higgins
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000648:ultrastructure; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000502:physiology; D019922:GAP-43 Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D007696:Kindling, Neurologic / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000033:anatomy & histology / Q000502:physiology* / Q000523:psychology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D013569:Synapses / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D019922:GAP-43 Protein; D008869:Microtubule-Associated Proteins; D016708:Synaptophysin