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.CD38<sup>null</sup>, scid<sup>null</sup> 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>|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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|
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.