Updated 5 January 2009

General Information

Transgene: A targeting vector containing a phosphoglycerol kinase promoter driven neomycin resistance gene was inserted into exon 2 of the endogenous gene, replacing approximately 500 base pairs within the exon including the first three potential start codons. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females.

Mutation: Targeted

Promoter: Phosphoglycerol kinase (PGK)

Breeding: Heterozygotes were backcrossed to C57BL/6J mice for more than 10 generations. TJL mating, Heterozygote x Heterozygote (Female x Male). Homozygotes are fertile but poor breeders, while heterozygous mice have no breeding problems.

Strain: B6.129-Apbb1^tm1Quhu /J

Phenotype

Neuropathological Analysis:

The endogenous full-length 97 kDa protein (p97) is not expressed in brain tissue from homozygous mice.

The 60 kDa (p60) N-terminal truncated isoform of the endogenous protein is expressed in mutant and wildtype brain tissue, with mutant mice exhibiting 4-5-fold greater levels.

Behavioral Phenotype:

Homozygous mice are viable and normal in size and display no physical or histopathologically demonstrable abnormalities.

Homozygous null mice exhibit slower learning rates on both aversive and spatial memory tasks and severe impairments in spatial memory extinction during relearning.

Heterozygotes have an intermediate phenotype, except with normal spatial memory extinction during relearning.

Availability

Contact: The Jackson Lab, cryopreserved, stock #005708. Companies or for-profit entities requires a license prior to shipping.

References

Primary:

Wang B, Hu Q, Hearn MG, Shimizu K, Ware CB, Liggitt DH, Jin LW, Cool BH, Storm DR, Martin GM. Isoform-specific knockout of FE65 leads to impaired learning and memory. J Neurosci Res 2004;75(1):12-24. Abstract

Associated:

Hu Q, Wang L, Yang Z, Cool BH, Zitnik G, Martin GM. Endoproteolytic cleavage of FE65 converts the adaptor protein to a potent suppressor of the sAPPalpha pathway in primates. J Biol Chem. 2005 Apr 1;280(13):12548-58. Epub 2005 Jan 12. Abstract

Pardossi-Piquard R; Petit A; Kawarai T; Sunyach C; Alves da Costa C; Vincent B; Ring S; D'Adamio L; Shen J; Muller U; St George Hyslop P; Checler F. Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP. Neuron 2005;46(4):541-54. Abstract