This targeted mutation of the calcium response factor (Carf) gene displays abnormal performance in reversal learning, remote memory and conditioned fear tests and may be useful in the study of learning and memory.
Anne West, Duke University Medical Center
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical abnormalities. Mice test similar to wild-type in a SHIRPA screen for neurological abnormalities, however, in the Morris water maze test for reversal learning, mice exhibit an enhanced ability to find the new platform. Novel object recognition tests reveal intact short-term and long-term memory, but impairment in cortical-regulated remote memory. Mice exhibit a delay in extinction learning in fear conditioning tests.
This mutant mouse strain may be useful in studies of learning and memory.
A targeting vector was designed to place an FRT-flanked neomycin resistance cassette followed by a loxP site 133 bp 5' to the beginning of exon 8 and a loxP site at the end of exon 8. The construct was electroporated into 129S4/SvJae derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were mated to C57BL/6J mice. To remove the FRT neo cassette, mice were crossed to 129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J. To remove loxP-flanked exon 8, mice were crossed to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J.
Mice retain a single loxP and an FRT site downstream of exon 7. Progeny from this mating were intercrossed prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1.1, Anne West|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1.1, Anne West; Carftm1.1Aew|
|Gene Symbol and Name||Carf, calcium response factor|
|Gene Synonym(s)||NYD-SP24; ALS2CR8; Als2cr8|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A FRT-flanked Neo cassette and a single loxP site were placed 5' to exon 8 and a second loxP site was placed at the 3' the end of exon 8. The selection cassette and exon 8 were removed by flp and cre mediated recombination respectively. A shorter mRNA is produced consistent with the deletion of exon 8.|
|Mutations Made By|| |
Anne West, Duke University Medical Center
While maintaining a live colony, these mice can be bred as heterozygotes or homozygotes. The donating investigator maintained this strain as a heterozygous mating.
When using the B6;129S4-Carftm1.1Aew/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012623 in your Materials and Methods section.
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