Updated 5 January 2009
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.
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.
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
Homozygous mice are viable and normal in size and display no physical or histopathologically
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.
Contact: The Jackson
Lab, cryopreserved, stock #005708. Companies or for-profit entities requires
a license prior to shipping.
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
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.
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.