Congenic NOD/Lt mice homozygous for the Cd38tm1Lnd mutation (Commonly referred to as NOD.Cd38 short) are viable, fertile and exhibit accelerated Type 1 diabetes onset in females and males. This acceleration has been correlated with further impairment of an already subnormal immunoregulatory network. Regulatory T-cells from these mice are more sensitive to NAD-mediated apoptosis when compared to NOD/Lt controls. Similarly, NOD-characteristic reductions in NKT cell numbers are further exacerbated in homozygous NOD.Cd38tm1Lnd mutant mice. Although CD38 is reportedly required for normal pancreatic beta cell responses to glucose, this was not confirmed in congenic, doubly homozygous NOD.PkrdcscidCD38tm1Lnd mutant mice.
NOD.129P2(B6)-Cd38tm1Lnd/LtJ mice are valuable for understanding how systemic NAD metabolism can be used to alter immunoregulatory networks.
CD38 (ADP ribosyl cyclase/cADPR hydrolase) is a Nicotinamide Adenine Dinucleotide (NAD) utilizing ectoenzyme involved in calcium mobilization. It is ubiquitously expressed to varying degrees on both hematopoietic and non-hematopoietic tissues. NAD released from target cell lysis that is not utilized by CD38 can elicit T cell apoptosis through the activity of another NAD-utilizing and T cell-specific ectoenzyme, ADP ribosyltransferase.A construct containing a neomycin expression cassette replacing exon 2 and 3 of Cd38 was transfected into E14-1 (129P2/OlaHsd-derived) embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. As reported by Cockayne et al, 1998, chimeric founders were initially mated to C57BL/6 and intercrossed to generate homozygotes (B6.129P2-Cd38tm1Lnd). B6.129P2-Cd38tm1Lnd/J (stock# 3727)homozygote mice were subsequently mated to NOD/Lt for 11 generations prior to making homozygous. Marker assisted analysis indicates all known Idd loci are NOD/Lt in origin. In 2005, the T1DR received NOD.129P2(B6)-Cd38tm1Lnd/LtJ at generation N11F5.
|Allele Name||targeted mutation 1, Frances E Lund|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CD38-; CD38null; Cd38tm1Lud|
|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
The accelerated diabetes development in NOD.129P2(B6)-Cd38tm1Lnd/LtJ homozygous breeding stock is not significantly retarded by either CFA or alpha galactosylceramide prophylaxis.
When using the NOD.CD38null mouse strain in a publication, please cite the originating article(s) and include JAX stock #004311 in your Materials and Methods section.
|Homozygous for Cd38<tm1Lnd>|
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.
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|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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