STOCK Gt(ROSA)26Sor^{tm1(RARA*)Soc}/HsvJ

Stock number: 029812
Product name: R26^RAR403
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

Expression of a dominant negative RAR403 protein is prevented in these R26^RAR403 mice until crossed to a strain expressing Cre recombinase under the control of a promoter of interest. This strain may be useful when studying nervous system development.

Detailed description

R26^RAR403 mice contain a loxP-flanked STOP sequence upstream of a mutated human retinoic acid receptor, alpha (RARA) gene. The retinoic acid receptor signaling pathway plays a role in regulating nervous system development. It has also been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. The RAR403 mutation present in these mice causes truncation of the RARA protein. Widespread expression of RAR403 is prevented by a strong transcriptional stop sequence. When bred to mice that express Cre recombinase under the control of a promoter of interest, the loxP-flanked STOP sequence is removed, and RAR403 is expressed in cre-expressing cells. The resulting mutant receptor behaves as a dominant negative receptor which blocks endogenous retinoic acid signaling. It is not known if expression of RARA403 interferes with signaling by any other nuclear receptors. Homozygous mice are viable and fertile.

When crossed to B6.129P2(Cg)-Foxg1^tm1(cre)Skm/J (Stock No. 006084) expressing Cre Recombinase in the telencephalon, resulting offspring exhibit a a 15% decrease in cell proliferation of dorsal telencephalic progenitors at E10.5. Also, there is and 5-fold increase in apoptosis in the pallium and 4-fold increase in the subpallium.

Development

A targeting vector was designed placing a loxP-flanked STOP (containing a neomycin resistance (neo) cassette and 3 polyadenylation sequences) upstream of the human retinoic acid receptor, alpha (RARA) gene. A mutation was inserted at amino acid 403, resulting in a stop codon. This construct was inserted into the Gt(ROSA)26Sor locus via electroporation into embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric males were bred to wildtype females and the resulting R26^RAR403 mice were maintained on a mixed background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Gt(ROSA)26Sor^{tm1(RARA*)Soc}
Name: targeted mutation 1, Shanthini Sockanathan
MGI accession ID: MGI:3793772
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Dominant negative; Inserted expressed sequence; Humanized sequence
Synonyms: dnRAR-alpha; R26^RAR403; Rara403 conditional
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Marker synonyms: beta geo; Gtrgeo26; Gtrosa26; R26; ROSA26; SETD5-AS1; Thumpd3as1
Chromosome: 6
Strain of origin: Not Specified
Expressed genes: RARA,retinoic acid receptor alpha,human
Site of expression: When bred to mice that express Cre recombinase under the control of a promoter of interest, the loxP-flanked STOP sequence is removed, and RAR403 is expressed in cre-expressing cells.
Molecular note: A floxed neo-STOP cassette followed by a dominant negative form of human RARA (RAR403) was inserted into the ROSA locus. Cre mediated removal of the neo-STOP cassette is necessary for expression of RAR403.