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Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse

1998; Elsevier BV; Volume: 85; Issue: 1 Linguagem: Inglês

10.1016/s0306-4522(97)00598-8

1873-7544

Richard B. Anderson, Jen Barnes, T.V.P. Bliss, Donald P. Cain, Karine Cambon, Heather A. Davies, M.L. Er̀rington, L.A. Fellows, Richard A. Gray, Tim Hoh, M.G. Stewart, Charles H. Large, Guy A. Higgins,

Retinal Development and Disorders

Using apolipoprotein E knockout mice derived from the Maeda source [Piedrahita J. A. et al. (1992) Proc. natn. Acad. Sci. U.S.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.