These mice carry a targeted knock-out allele of the mouse Ece2 gene. Homozygotes display deficits in learning and memory. Mutations in this locus have been reported in Alzheimer's disease patients.
William C Wetsel, Duke University Medical Center
Mutations in ECE2 (endothelin converting enzyme 2) have been reported in Alzheimer's disease patients.
These mice carry a targeted knock-out of the mouse Ece2 gene. The homozygous mutant mice are born in standard Mendelian ratios from heterozygous breedings. Homozygous mice develop normally, are healthy into adulthood, are fertile in both sexes, and live a normal life span.
The physical appearance, autonomic reflexes, motor co-ordination, balance, locomotor activity and spontaneous emotional responses appear normal in the knock-out mice. However, these mutants display deficits in learning and memory as evidenced by marked impairment in the Morris water maze. Homozygous knock-out mice are also deficient in object recognition memory where they show delays in discerning changes in object location and in recognizing the introduction of a novel object.
The mutants are impaired in social transmission of food preference where they show poor short-term memory and perturbations in long-term memory; the latter can be ameliorated by reminder cues.
Homozygous knock-out mice show decreased response to a single injection of morphine in hot-plate and tail-flick tests, but they develop tolerance to morphine more rapidly than wildtype controls and show fewer signs of naloxone-precipitated withdrawal.
The exons encoding the zinc-binding catalytic domain were replaced with a neomycin resistance cassette via homologous recombination in 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Resultant chimeric males were bred with C57BL/6J females. This strain was backcrossed to C57BL/6 for approximately 5 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Masashi Yanagisawa|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ece2, endothelin converting enzyme 2|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exons 14 and 15, the latter of which encodes the essential conserved zinc-binding motif, were replaced with a neomycin selection cassette. RT-PCR analysis of total RNA extracted from homozygous mutant brain tissue showed an absence of expression.|
Homozygotes and heterozygotes are viable and fertile.
When using the ECE-2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #030639 in your Materials and Methods section.