Shcbp1-/- KO mice develop attenuated disease levels in an EAE model of autoimmunity. They may be useful in studies related to CD4+ T cell effector function.
Kodi S. Ravichandran, University of Virginia
Shcbp1-/- KO mice lack exons 4-6 of the Shc SH2-domain binding protein 1 (Shcbp1) gene, abolishing gene function. ShcBP1 binds to the ShcA adaptor protein which is a regulator of T cell development and proliferation. ShcBP1 has also been linked to cell proliferation, embryonic development, growth factor signaling, and tumorigenesis. Homozygotes are viable and fertile. In a mouse model of Experimental autoimmune encephalomyelitis (EAE), which depends on CD4+ T cell function, Shcbp1-/- mice have reduced disease severity and improved survival with no effect on the development or the proliferative state of activated T cells.
The floxed version of this allele is available as Stock No. 025770.
C57BL/6N-Atm1Brd-derived JM8A3.N1 embryonic stem (ES) cells containing a targeted mutation of the Shc SH2-domain binding protein 1 (Shcbp1) gene were obtained from The European Conditional Mouse Mutagenesis Program (EUCOMM). The Shcbp1 gene has a frt-flanked and loxP-flanked neomycin resistance (neo) cassette upstream of exon 4, and a third loxP site downstream of exon 6. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric mice were bred C57BL/6J. Offspring were bred with B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 005703) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. Mice were subsequently bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J cre transgenic mice (Stock No. 003724) to delete exons 4-6. Shcbp1-/- mice were maintained on a C57BL/6J background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1d, Wellcome Trust Sanger Institute|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Shcbp1, Shc SH2-domain binding protein 1|
|Strain of Origin||C57BL/6N-Atm1Brd|
|Molecular Note||The L1L2_Bact_P cassette was inserted at position 4750268 of Chromosome 8 upstream of the critical exon(s) (Build GRCm38). The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted downstream of the targeted exon(s) at position 4748418. The critical exons are thus flanked by loxP sites. The lacZ and neomycin segments were excised with germline Flp recombinase, leaving exons 4 and 6 flanked by loxP sites. Then animals were crossed with a germline Cre strain to delete exons 4 through 6. Further information on targeting strategies used for this and other IKMC alleles can be found at http://www.informatics.jax.org/mgihome/nomen/IKMC_schematics.shtml.|
When maintaining a live colony, homozygous mice may be bred together.
When using the B6(Cg)-Shcbp1tm1d(EUCOMM)Wtsi/RaviJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #025771 in your Materials and Methods section.