The nArgBP2- knockout allele has a deletion of the neuronal-specific exon (NSE; exon 16) of the Sorbs2 gene. As the deleted exon characterizes the neuronal isoform (nArgBP2), these mice may be useful in studying the loss of nArgBP2 in dendritic development, memory formation and neural circuits underlying the behavioral abnormalities.
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; exon 16) that is absent in other ArgBP2 isoforms. Additionally, the Sorbs2 NSE can promote nArgBP2 targeting into dendritic spines.
The nArgBP2- knockout allele has the neuronal-specific exon (NSE; exon 16) of the Sorbs2 gene deleted and replaced with a neomycin resistance cassette.
Heterozygous mice are viable and fertile with no reported abnormalities. The donating investigator reports that brain tissue from homozygous mice (nArgBP2-/-) have no detectable protein expression of the nArgBP2 isoform, whereas ArgBP2 isoform protein expression is elevated. To date (June 2016), the phenotype of nArgBP2-/- has not been fully characterized.
To review the phenotype of a mouse made to have global knockout of both the ArgBP2 and nArgBP2 isoforms (via removal of exon 12), see the description for the Sorbs2 floxed exon 12 mouse line (Sorbs2F; Stock No. 028600).
The nArgBP2- knockout allele was created by Dr. Guoping Feng (Massachusetts Institute of Technology). First, a targeting vector was designed to delete the neuronal-specific exon (NSE; exon 16) 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 C57BL/6J for germline transmission and to establish the colony. The resulting nArgBP2- colony was backcrossed to C57BL/6J inbred mice for at least ten generations prior to sending heterozygous 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 2, Guoping Feng|
|Allele Type||Targeted (Null/Knockout)|
|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 to delete the neuronal-specific exon (NSE; exon 16) and replaced with a neomycin resistance cassette. The investigator reports that brain tissue from homozygous mice have no detectable protein expression of the nArgBP2 isoform.|
When maintaining a live colony, heterozygous mice may be bred together, to wildtype littermates, or to C57BL/6J inbred mice (Stock No. 000664). To date (June 2016), the phenotype of homozygous mice has not been fully characterized.
When using the nArgBP2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #028609 in your Materials and Methods section.