Human Apolipoprotein E2, E3, and E4 Isoform-Specific Transgenic Mice: Human-like Pattern of GlialandNeuronal Immunoreactivity in Central Nervous System Not Observed in Wild-Type Mice

Authors: Xu P-T.¹; Schmechel D.^{1, 2}; Rothrock-Christian T.¹; Burkhart D.S.¹; Qiu H-L.¹; Popko B.³; Sullivan P.⁴; Maeda N.⁴; Saunders A.M.¹; Roses A.D.¹; Gilbert J.R.¹

Source: Neurobiology of Disease, Volume 3, Number 3, June 1996 , pp. 229-245(17)

Publisher: Academic Press

Abstract:

Apolipoprotein E (apoE) and its three major alleles (APOE2, E3,andE4) have been implicated in Alzheimer's disease and other neurological disorders. Little is known of the role apoE plays in normal brain function and pathology. To create a model to study apoE in brain, we have generatedAPOEtransgenic mice using microinjection of allele-specific human genomic fragments to establish founders which were then bred toAPOEknockout mice lacking a functional mouse apoE protein. This allows the study of apoE without interference from the endogenous mouseAPOEgene. Results demonstrate that transgenic lines have been established that transcribe and express apoE appropriately in brain, liver, and other tissues. High cholesterol levels found inAPOEknockout mice are substantially corrected in theAPOEtransgenic lines. ApoE immunoreactivity has been detected in glial cellsandselected classes of neurons in all three isoform-specific transgenics. This pattern of immunoreactivity is similar to that observed in nonhuman primates and man, and contrasts with the strictly glial staining pattern of normal rodents.

Language: English

Document Type: Research article

Affiliations: 1: Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina, 27710 2: Durham Veterans Administration Medical Center, Durham, North Carolina, 27705 3: Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599 4: Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599

Publication date: 1996-06-01

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• In this Subject: Neurology & Psychiatry
• By this author: Xu P-T. ;  Schmechel D. ;  Rothrock-Christian T. ;  Burkhart D.S. ;  Qiu H-L. ;  Popko B. ;  Sullivan P. ;  Maeda N. ;  Saunders A.M. ;  Roses A.D. ;  Gilbert J.R.

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