Sci. Aging Knowl. Environ., 29 October 2003
Vol. 2003, Issue 43, p. tg7
GENETICALLY ALTERED MICE
Apolipoprotein E4 Mice
||Apolipoprotein E4 mice.
||ES cells, 129P2/OlaHsd; blastocysts, C57BL/6. The resulting chimeric mice were bred to C57BL/6 mice, and the colony is maintained by homozygous matings.
||Human apolipoprotein E4 gene (apoE4).
|Type of change
||Polymerase chain reaction products encoding human apoE4 were subcloned into a Thy1.2 vector, and the DNA construct was microinjected into C57BL/6 mouse eggs.
|Nature of protein
||ApoE4 is a plasma protein involved in cholesterol transport and has been associated with atherosclerosis and Alzheimer's disease.
||The murine ApoE4 model has normal plasma cholesterol and triglyceride levels but altered quantities of plasma lipoprotein particles. These mice have delayed plasma clearance of very low density lipoprotein particles and develop altered plasma lipoprotein values and atherosclerotic plaques on an atherogenic diet. ApoE4 mice also have significant impairments in learning, memory, and exploratory behavior, as well as age-related excitotoxin-induced neurodegeneration, which is a key mechanism of neuronal injury in acute neurodegenerative processes such as head trauma and stroke.
|Corresponding human phenotype
||The apoE4 isoform occurs in about 14% of the human population and is associated with increased plasma cholesterol and an increased risk of coronary artery disease. The apoE4 isoform also correlates with an increased risk of Alzheimer's disease and a poor outcome after head trauma and stroke.
||M. Buttini, M. Orth, S. Bellosta, H. Akeefe, R. E. Pitas, T. Wyss-Coray, L. Mucke, R. W. Mahley, Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: Isoform-specific effects on neurodegeneration. J. Neurosci. 19, 4867-4880 (1999).
273 Hover Avenue
Germantown, NY 12526
Apoe4 targeted replacement mouse, order # 001549-M
Dr. Yadong Huang
Department of Pathology
University of California, San Francisco, CA 94143
||Online Mendelian Inheritance in Man (OMIM) entry for human Apolipoprotein E; APOE (*107741):
SAGE KE's Genes/Interventions (database): apoE4:
October 29, 2003
- F. M. Harris, W. J. Brecht, Q. Xu, I. Tesseur, L. Kekonius, T. Wyss-Coray, J. D. Fish, E. Masliah, P. C. Hopkins, K. Scearce-Levie, K. H. Weisgraber, L. Mucke, R. W. Mahley, Y. Huang, Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 100, 10966-10971 (2003). [Abstract/Free Full Text]
- C. Knouff, M. E. Hinsdale, H. Mezdour, M. K. Altenburg, M. Watanabe, S. H. Quarfordt, P. M. Sullivan, N. Maeda, ApoE structure determines VLDL clearance and atherosclerosis risk in mice. J. Clin. Invest. 103, 1579-1586 (1999).[Medline]
Apolipoprotein E4 Mice. Sci. SAGE KE 2003
(43), tg7 (2003).