General Information

Transgene: Human apoE2 gene with either PDGF-b or TF promoters were pronuclear injected into C57BL/6 fertilized oocytes.

Mutation:

Promoter: Platelet-derived growth factor b-chain (PDGF-b ) promoter, or the transferrin (TF) promoter.

Mouse strain: Original background: C57BL/6 (Tac), color: black. The PDGF-b apoE2 and the TF apoE2 transgenic mice were bred back to apoE-/-background.

Background strain of published and distributed model: C57Bl6 inbred and Swiss Webster outbred mice (Tac). ApoE-/- knockout mice (J)

Current Generation Number (Backcross, N and filial, F): Backcross apoE-/- N=2 Filial (current generation, 8/03) F6

Phenotype

Neuropathological analysis

In the PDGF transgenic mice, apoE2 synthesis was confined only in the brain, and was not detected in the serum. In the TF transgenic mice, apoE2 synthesis was observed in the brain as well as in the liver, and could be detected in the serum.

Immunohistochemical analysis showed that the PDGF apoE2 × apoE-/- and the TF apoE2 × apoE-/- mice express human apoE2 within the neocortex in hippocampal neurons and glial cells, respectively. The apoE synthesized by neurons or glial cells in the brain was secreted in the brain parenchyma as assessed by the brain organ culture experiments.

8-month-old apoE-/- mice showed a significant reduction in synaptophysin levels in their brains compared with the levels in the wild-type apoE+/+ mice, and PDGF/ TF apoE2 x apoE2-/- showed a significant increase (60%) in synaptophysin immunoreactivity as compared to the apoE-/- littermates of the same age.

Behavioral

Transgenic mice developed normally and showed no macroscopic difference compared to their nontransgenic littermates.

Availability

Licensing/academic distribution contact information:

Vassilis I. Zannis
Section of Molecular Genetics, Whitaker Cardiovascular Institute
Departments of Medicine and Biochemistry
Boston University School of Medicine
Boston, Massachusetts 02118
Telephone: (617) 638-5085
Fax: (617) 638-5141

Patents:

Reference

Primary:

Georgopoulos S, McKee A, Kan HY, Zannis VI. Biochemistry 41(30): 9293-301, 2002. Abstract