B6.129P2-Cd38^tm1Lnd/J

Stock number: 003727
Product name: CD38-
Research areas: Cancer Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These Cd38 knock-out mice exhibit impairments in glucose-induced increases in ADP-ribosyl cyclase/cyclic ADP-ribose (cADPR), intracellular calcium concentration, and insulin secretion. They are unable to mount an innate immune response to bacterial pathogens.

Detailed description

Mice homozygous for Cd38^tm1Lnd are viable, fertile and appear to be free from gross defects. Cd38 transcripts and protein product are not detected in these animals, nor are B lymphocytes responsive to the proliferative effects of anti-CD38 antibodies. NAD+ glycohydrolase activity in spleen, liver and brain is either markedly reduced or absent and a decrease in hapten-specific IgM, IgG1 and IgE responses is observed. Kato et al. recently published a targeted disruption in exon 1 of the Cd38 gene (J Biol Chem 274:1869-1872, 1999). Homozygous mutant mice show impairments in glucose-induced increases in ADP-ribosyl cyclase/cyclic ADP-ribose (cADPR), intracellular calcium concentration, and insulin secretion. These results support an essential role for CD38 in intracellular calcium mobilization by cADPR for insulin secretion. CD38 deficient mice are unable to mount an innate immune response to bacterial pathogens such as Streptococcus pneumoniae. In addition, CD38 dependent cADPR production is required for neutrophil chemotaxis and calcium signaling in response to the bacterially derived peptide fMLP.

Development

A targeting vector containing neomycin resistance and HSV-TK genes was used to disrupt Cd38 exons 2-3. The construct was transfected into 129P2/OlaHsd-derived E14-1 embryonic stem cells and selected cells were injected into C57BL/6J blastocysts.

Allele

Symbol: Cd38^tm1Lnd
Name: targeted mutation 1, Frances E Lund
MGI accession ID: MGI:1861803
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd38
Marker name: CD38 antigen
Chromosome: 5
Strain of origin: 129P2/OlaHsd
Molecular note: A neomycin selection cassette replaced a genomic fragment containing exons 2 and 3, which encode the putative active site of the encoded protein. Homozygous mice lacked transcripts derived from this allele (data not shown). Flow cytometry analysis on splenocytes derived from homozygous mice confirmed that no detectable protein was expressed on the cell surface.