General Information

Transgene:   The 6.0 kbps promoter fragment was subcloned into the Bam HI/XbaI site of pCMV. A 1.6 kbp fragment containing the human b-globin splice fragment was subcloned.  A cDNA for ApoE3 was reverse transcribed and converted to ApoE4 by site-directed mutagenesis. 

Mutation:   ApoE4 cDNA was mutated at residue 28 from Leu to Pro by site specific mutagenesis.

Promoter:  rat GFAP gene promoter. , The 990 bp ApoE4 fragment was subcloned downstream from GFAP promoter and upstream from the b-globin site.

Mouse strain:     cDNA were microinjected into the male pronuclei of B6D2FI zygote.  Zygotes were reimplanted into pseudopregnant B6CBAFI females.  Crossed twice with wt C57BL/6 mice.

Phenotype

Neuropathological analysis

Homozygous ApoE4(C112R) contained total ApoE proteins 3.5 fold the endogenous ApoE in wt.

Homozygous ApoE4(L28P; C112R) contained total ApoE proteins 2 fold the endogenous ApoE in wt.

Quantitative Western for synaptic proteins, cytoskeletal protein tau, PkC, and APP show no significant change from wt.

Behavioral

In either passive avoidance task and an active avoidance task, neither Tg mice were different from the wt.

Availability

Licensing/academic distribution contact information:

Gerda Huber gerda.huber_trottmann@roche.com

Patents: None

Reference

Primary:

Huber G, Marz W, Martin JR, Malherbe P, Richards JG, Sueoka N, Ohm T, Hoffmann MM. Characterization of transgenic mice expressing apolipoprotein E4(C112R) and apolipoprotein E4(L28P; C112R). Neuroscience 2000;101(1):211-8. Abstract.