B6.Cg-Cacna1f^tm1Sdie/J

Stock number: 017760
Research areas: Cell Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools, Sensorineural Research

Description

These I756T+neo mice carry the I756T point mutation in exon 17 of the Cacna1f, calcium channel, voltage-dependent, alpha 1F subunit, (756 is the mouse equivalent to residue 745 in human CACNA1F) as well as a FRT flanked NEO selection cassette and loxP sites flanking exons 14 through 17. This mutant mouse strain may be useful in studies of calcium channelopathies, incomplete congenital stationary night blindness, photoreceptor electrophysiology, and the role of the Cav1.4 channel in survival of naive T cells.

Detailed description

L-type voltage dependent calcium channels are a primary means calcium ion entry into the cell. The alpha 1F subunit makes up the central pore forming portion of the L-type voltage dependent calcium channel, Cav1.4. Genetic defects in Cav1.4 can cause human incomplete congenital stationary night blindness. These mice carry 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), a FRT site flanked NEO selection cassette and loxP sites flanking exons 14 through 17 (including the selection cassette). Female mice that are homozygous and male mice that are hemizygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. The Donating Investigator reports that the selection cassette appears to interfere with gene expression (splicing), and that mutant mice exhibit abnormal retinal immunohistochemistry results. This strain was used to generate a knock out strain (Stock No. 017761) and a strain expressing the I756T point mutation (Stock No. 017762).

Development

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 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.

Allele

Symbol: Cacna1f^tm1Sdie
Name: targeted mutation 1, Susanne tom Dieck
MGI accession ID: MGI:3838716
Generation method: Targeted
Attributes: Humanized sequence
Marker symbol: Cacna1f
Marker name: calcium channel, voltage-dependent, alpha 1F subunit
Marker synonyms: AIED; Cav1.4; Cav1.4alpha1; COD3; COD4; CORDX; CORDX3; CSNB2; CSNB2A; CSNBX2; JM8; JMC8; OA2; Sfc17
Chromosome: X
Strain of origin: B6.Cg-Thy1^a
Molecular note: A loxP site was inserted into intron 13, and an FRT site flanked neomycin resistance gene cassette and a second loxP site were inserted into intron 17. Exon 17 contains nucleotide substitutions that result in the amino acid substitution of isoleucine with threonine at position 756 (p.I756T) which corresponds to the same human mutation found in patients with an X-linked retinal disorder.