129S6.129X1(B6)-Ptprc^tm1Weis/J

Stock number: 007172
Product name: CD45 E613R
Strain synonyms: C45 E613R/129.F9
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

B, T, and myeloid cells in mice homozygous for this targeted point mutation are hyperresponsive to stimulation, and B cell development is skewed to the B1 cell lineage. A mild lymphoproliferative disorder is developed but mice develop low titer or no autoantibodies.

Detailed description

Mice homozygous for this targeted point mutation are viable and fertile. The phenotype of this mutation, which inactivates the inhibitory wedge of the protein, is dependent upon the genetic background. On the 129S6 background, B, T, and myeloid cells are hyperresponsive to stimulation at a biochemical and cellular level. B cell development is skewed to the B1 cell lineage. A mild lymphoproliferative disorder develops, but the autoantibodies associated with the mixed C57BL/6 and 129 background do not develop (or do so at low titer). Cell surface expression of the protein is indistinguishable from wildtype as determined by flow cytometry of hematpoietic lineages in bone marrow, lymph node, spleen, thymus, peritoneal lavage, and peripheral blood.

Development

A targeting vector carrying the glutamate 613 (E613R) mutation in exon 18 and a loxP-flanked neomycin resistance cassette in the downstream intron was transfected into 129X1/SvJ-derived JM-1 embryonic stem (ES) cells. Targeted clones were microinjected into C57BL/6 blastocysts and mice derived from the resultant lines were bred to a C57BL/6 background Actb-Cre transgenic mouse to eliminate the neomycin resistance cassette. This line was crossed to C57BL/6, and later backcrossed to 129S6/SvEvTac for nine generations by the donating laboratory.

Allele

Symbol: Ptprc^tm1Weis
Name: targeted mutation 1, Arthur Weiss
MGI accession ID: MGI:3027340
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: CD45 E613R; Cd45^w; Wedge
Marker symbol: Ptprc
Marker name: protein tyrosine phosphatase, receptor type, C
Chromosome: 1
Strain of origin: 129X1/SvJ
Molecular note: To recapitulate a mutation in the orthologous human gene that disrupts the inhibitory wedge, a glutamate to arginine substitution at codon 613 (E613R) was engineered in exon 18 and incorporated at the endogenous locus via homolgous recombination. A single loxP site remained in intron 18 after the floxed neo cassette was excised.