B6.129P2-Cd1d1^tm2Aben/J

Stock number: 016930
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

Sequence encoding the cytoplasmic tail that governs steady-state accumulation of CD1D1 (CD1d1 antigen) protein in endosome compartments was deleted in these targeted mutation mice. Homozygotes show multiple and selective abnormalities in intracellular trafficking, antigen presentation, and T cell development.

Detailed description

Sequence encoding the cytoplasmic tail that governs steady-state accumulation of CD1D1 (CD1d1 antigen) protein in endosome compartments was deleted in these targeted mutation mice. A neomycin gene was left in the 3' untranslated region of Cd1d1. Homozygotes show multiple and selective abnormalities in intracellular trafficking of CD1D and lipid antigen presentation, as well as natural killer T (NKT) cell development. On average, the mutant CD1-TD protein is expressed on the cell surface at 40% higher density than with wildtype protein in thymocytes, B cells and dendritic cells. Confocal microscopic analysis shows that the abundant intracellular stores of CD1D normally found in lysosome-associated membrane protein 1-positive (LAMP-1⁺) late endosomes and lysosomes is markedly depleted. A marked reduction in the number of Vα14 natural killer T (NKT) cells in the thymus and peripheral tissues including the spleen and liver was also noted. These mice may be helpful in studies of CD1D trafficking and antigen presentation pathways as well as the development of CD1D-restricted T cells.

Development

A vector incorporating a deletion of the nucleotides encoding the SAYQDIR carboxy-terminus (cytoplasmic tail) segment of the targeted gene followed by a floxed neomycin resistance cassette was introduced to 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. The donating investigator reported that this strain was backcrossed to C57BL/6 (Taconic) for 12 generations by the donating laboratory (see SNP note below).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository (after breeding once to C57BL/6NJ). While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the donating investigator backcrossed the mice to the C57BL/6J inbred mice available from Taconic prior to sending to The Jackson Laboratory Repository.

Allele

Symbol: Cd1d1^tm2Aben
Name: targeted mutation 2, Albert Bendelac
MGI accession ID: MGI:5056289
Generation method: Targeted
Marker symbol: Cd1d1
Marker name: CD1d1 antigen
Chromosome: 3
Strain of origin: 129P2/OlaHsd
Molecular note: The nucleotides encoding the SAYQDIR carboxy-terminus (cytoplasmic tail) segment were deleted. A floxed neo cassette was inserted downstream of the last exon.