These mice carry the I756T point mutation in exon 17, and loxP sites flanking exons 14 through 17, of the Cacna1f (calcium channel, voltage-dependent, alpha 1F subunit). This mutant mouse strain may be useful in studies of calcium channelopathies, an inherited retinal disorder, photoreceptor electrophysiology, and the role of the Cav1.4 channel in survival of naive T cells.
The mouse I756T point mutation is equivalent to an I745T mutation in the human CACNA1F gene that is responsible for an inherited retinal disorder related to, but distinct from, X-linked incomplete congenital stationary night blindness in a New Zealand family. These mice carry the I756T point mutation in exon 17, that results in an amino acid substitution of threonine for isoleucine at position 756, and loxP sites flanking exons 14 through 17. Female mice that are homozygous and male mice that are hemizygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The Donating Investigator reports that this targeted mutation is a gain-of-function allele in an in vitro expression system. This strain was generated from breeding (Stock No. 017760) mice to a FLP recombinase expressing strain.
A targeting vector was used to insert a point mutation in exon 17 that results in an amino acid substitution of threonine for isoleucine at position 756, the mouse equivalent to residue 745 in human CACNA1F, FRT site flanked PGKneo cassette into intron 17, as well as loxP sites into introns 13 and 17. A portion of intron 14 was also deleted. The construct was electroporated into C57BL/6 derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were then crossed to FLP recombinase-expressing mice on the C57BL/6 background to remove the selection cassette. Mice that retained the point mutation in exon 17 and the loxP sites flanking exons 14 through 17 were then bred to C57BL/6 mice to remove the FLP recombinase allele.
|Allele Name||targeted mutation 1.2, Susanne tom Dieck|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Cacna1f, calcium channel, voltage-dependent, alpha 1F subunit|
|Strain of Origin||B6.Cg-Thy1a|
|Molecular Note||Cacna1ftm1Sdie mice were crossed with FLP recombinase-expressing mice to remove the neomycin selection cassette. This allele retains the I756T point mutation in exon 17 and the loxP sites flanking exons 14 through 17.|
|Mutations Made By|| |
When maintaining a live colony, homozygous females may be bred to hemizygous males(mutation is X-linked).
When using the B6.Cg-Cacna1ftm1.2Sdie/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017762 in your Materials and Methods section.