C57BL/6-Ptprc^ltng/J

Stock number: 016091
Research areas: Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These lightning mice possess an ENU-induced point mutation (F503S) in the Ptprc gene and may be useful in studying the differential regulation of TCR signaling by altered CD45 expression levels.

Detailed description

These lightning mice possess an ENU-induced point mutation (F503S) in the protein tyrosine phosphatase, receptor type, C (Ptprc), gene. Homozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Ptprc encodes CD45, a protein tyrosine kinase which is expressed in nucleated hematopoietic cells and is required for their activation. CD45 is also required for T cell receptor (TCR) signaling and T cell development. These mice contain only 15% of the normal level of CD45 expression on the surface of nucleated hematopoietic cells, without altering splicing of transcript isoforms. These mutant mice may be useful in studying the differential regulation of TCR signaling by altered CD45 expression levels.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice, a genetic screen was utilized to identify lightning mice, exhibiting reduced expression of CD45 on the surface of all nucleated hematopoietic cells. Using a candidate gene approach a mutation was identified in the protein tyrosine phosphatase, receptor type, C (Ptprc), gene. Sequencing of Ptprc identified a T to C point mutation resulting in a phenylalanine to serine missense mutation (F503S). These mice were maintained on a coisogenic C57BL/6J background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Ptprc^ltng
Name: lightning
MGI accession ID: MGI:4441612
Generation method: Chemically induced (ENU)
Marker symbol: Ptprc
Marker name: protein tyrosine phosphatase, receptor type, C
Chromosome: 1
Strain of origin: C57BL/6
Molecular note: ENU induced at T to C transition that results in the amino acid substitution of serine for phenylalanine at position 503 (F503S). Flow cytometry confirmed that protein half-life is reduced.