The ArgBP2 exon12 flox allele (Sorbs2F) has loxP sites flanking exon 12 of the Sorbs2 gene. Removal of the floxed sequence creates a null allele. As the floxed exon is conserved in nearly all ArgBP2 isoforms, these mice may be useful in studying non-neuronal ArgBP2 (congenital heart disease/cardiology and cancer metastasis/oncology research) as well as neuronal ArgBP2 (nArgBP2; dendritic development and memory formation).
Guoping Feng, Massachusetts Institute of Technology
Through alternative RNA splicing, Sorbs2 encodes multiple transcripts; and exon 12 (encoding the Sorb C-terminal domain) is predicted to be present in most transcripts.
Several ArgBP2 isoforms are widely expressed (in heart, pancreas, colon, etc.). In the brain, only the neuronal isoform (nArgBP2) is highly expressed (including cortex, amygdala and DG), and is characterized by the presence of a neuronal-specific exon (NSE; downstream of exon 12) that is absent in other ArgBP2 isoforms. Additionally, the Sorbs2 NSE can promote nArgBP2 targeting into dendritic spines.
The Sorbs2F allele has loxP sites flanking exon 12 of the Sorbs2 gene. Mice homozygous for the floxed allele (Sorbs2F/F) are viable and fertile with no reported abnormalities.
When bred to mice that express Cre recombinase, the resulting offspring may be useful in generating a tissue-specific Sorbs2 knockout. For example, breeding to germline Cre-expressing mice (Stock No. 019099) generates the Sorbs2 global knockout allele (Sorbs2-). The phenotype of homozygous knockout (Sorbs2-/-) mice backcrossed six generations onto the C57BL/6J inbred background is described below. Sorbs2-/- have ~40-60% lethality in the first week, with surviving animals exhibiting reduced dendritic complexity, decreased excitatory synaptic transmission, impaired acoustic startle response and defective long-term memory. Overall brain morphology is not affected by Sorbs2-deficiency. No ArgBP2/nArgBP2 protein expression from the knockout allele is observed in heart or brain (western blot using antibodies against conserved domains downstream of the Sorb domain). Mice harboring the Sorbs2- allele may be useful in studying the neural circuits underlying these behavioral phenotypes.
Of note, mice harboring a knockout allele that deletes the Sorbs2 neuronal isoform-specific exon 16 (nArgBP2-) are available as Stock No. 028609, and may be useful to study the loss of nArgBP2 in dendritic development, memory formation and neural circuits underlying the behavioral abnormalities.
The ArgBP2 exon12 flox allele (Sorbs2F) was created by Dr. Guoping Feng (Massachusetts Institute of Technology). First, a targeting vector was designed with a loxP::frt-SV40 promoter-Neo-pA-frt cassette 389 bp upstream of exon 12, and a loxP site 676 bp downstream of exon 12 of the sorbin and SH3 domain containing 2 gene (Sorbs2 ; ArgBP2) on chromosome 8. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric mice were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J (Stock No. 005703) for germline deletion of the frt-flanked neo cassette. The resulting Sorbs2F mice were backcrossed to C57BL/6J inbred mice for at least ten generations (and the Flp-expressing transgene was removed) prior to sending males with black coat color to The Jackson Laboratory Repository in 2016. 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).
Of note, the donating investigator reports that, at least once during backcrossing, a heterozygous female was bred to a C57BL/6J inbred male (thus the Y chromosome of the congenic strain is of C57BL/6J origin).
|Allele Name||targeted mutation 1.1, Guoping Feng|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Sorbs2, sorbin and SH3 domain containing 2|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||The targeting vector was designed with a loxP::frt-SV40 promoter-Neo-pA-frt cassette 389 bp upstream of exon 12, and a loxP site 676 bp downstream of exon 12. Flp-mediated recombination removed the FRT-flanked neo cassette.|
When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). Alternatively, homozygous mice may be bred together.
When using the Sorbs2F mouse strain in a publication, please cite the originating article(s) and include JAX stock #028600 in your Materials and Methods section.
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