Combining the Prkdcscid mutation with the Cd38tm1Lnd targeted allele in these mice completely prevents Type 1 diabetes, which otherwise would develop in mice carrying only the Cd38tm1Lnd targeted allele.
Dr. Edward Leiter, The Jackson Laboratory
CD38 is an ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase. This ubiquitously expressed ectoenzyme is the major NAD hydrolase in mice. NOD/Lt mice homozygous for the Cd38tm1Lnd targeted allele develop accelerated Type 1 diabetes associated with an ART2 (T cell ADP-ribosyltransferase)-dependent and NAD-mediated loss of regulatory CD4+CD25+ Foxp3+ and CD4+iNKT cells (Chen, J. et al 2006; Chen, Y.G et al 2006). Combining the Prkdcscid mutation with the Cd38tm1Lnd targeted allele completely prevents diabetes development. For investigators wishing to study the role of CD38 in beta cell biology, the presence of the Prkdcscid allele provides insultis-free islets for analysis. Congenic, doubly homozygous NOD.Cd38tm1Lnd Prkdcscid mutant mice exhibit no significant difference in glucose tolerance when compared to NOD or NOD. Prkdcscid, thus not supporting a previous report(Okamoto, H. and S. Takasawa; 2002) that CD38 is required for normal pancreatic beta cell glucose responsiveness. NOD.Cg-Cd38tm1LndPrkdcscid/LtJ mice offer an alternative means for maintaining the targeted CD38 allele on the NOD background. Without the Prkdcscid mutation, the accelerated diabetogenesis produced by CD38 deficiency makes colony propagation difficult.
NOD mice homozygous for the Cd38tm1Lnd allele (stock# 004311) were crossed to NOD.Prkdcscidmice for 2 generations, prior to making homozygous for scid and the CD38 targeted mutation. FACS analysis, of peripheral blood cells, confirms the absence of mature T and B cells and CD38 deficiency. In 2006, the T1DR received NOD.Cg- NOD.Cg-Cd38tm1LndPrkdcscid/Lt at generation [N2F3p].
|Allele Name||targeted mutation 1, Frances E Lund|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CD38-; CD38null|
|Gene Symbol and Name||Cd38, CD38 antigen|
|Gene Synonym(s)||ADPRC 1; ADPRC1; CD38 antigen, related sequence 1; Cd38-rs1; Cd38-rs1|
|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.|
|Mutations Made By|| |
Debra Cockayne, Roche Bioscience
|Allele Name||severe combined immunodeficiency|
|Allele Synonym(s)||SCID; scid|
|Gene Symbol and Name||Prkdc, protein kinase, DNA activated, catalytic polypeptide|
|Gene Synonym(s)||AI326420; AU019811; DNA-PK; DNA-PKcs; DNAPDcs; DNAPK; DNPK1; DOXNPH; HYRC; HYRC1; IMD26; XRCC7; doxorubicin nephropathy; dxnph; dxnph; expressed sequence AI326420; expressed sequence AU019811; p350; scid; severe combined immunodeficiency; slip|
|Site of Expression||T and B lymphocytes.|
|Strain of Origin||C.B-17|
|Molecular Note||A T-to-A transversion point mutation at a position corresponding to codon 4095 created a premature stop codon.|
When using the NOD.CD38null, scidnull mouse strain in a publication, please cite the originating article(s) and include JAX stock #005345 in your Materials and Methods section.
|Homozygous for Cd38<tm1Lnd>, Homozygous for Prkdc<scid>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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