Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N12F3+5   Donating Investigator Frances Lund,   The Trudeau Institute

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.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Cd38^tm1Lnd allele

005347	NOD.129(B6)-Cd38tm1Lnd Art2atm1Fkn Art2btm1Fkn/Lt
004311	NOD.129P2(B6)-Cd38tm1Lnd/LtJ
005345	NOD.Cg-Cd38tm1Lnd Prkdcscid/LtJ

View Strains carrying   Cd38^tm1Lnd     (3 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Cd38^tm1Lnd/Cd38^tm1Lnd

        B6.129P2-Cd38^tm1Lnd

• endocrine/exocrine gland phenotype
• abnormal islet of Langerhans morphology (MGI Ref ID J:116576)
  • disrupted islet architecture is observed
  • glucagon-containing alpha cells are distributed diffusely between beta cells, whereas in wild-type islets, alpha cells are exclusively in the islet mantle
• abnormal pancreatic beta cell morphology (MGI Ref ID J:116576)
  • small but significant decrease in beta cell mass is observed under normal diet and high-fat feeding relative to controls
• digestive/alimentary phenotype
• abnormal islet of Langerhans morphology (MGI Ref ID J:116576)
  • disrupted islet architecture is observed
  • glucagon-containing alpha cells are distributed diffusely between beta cells, whereas in wild-type islets, alpha cells are exclusively in the islet mantle
• abnormal pancreatic beta cell morphology (MGI Ref ID J:116576)
  • small but significant decrease in beta cell mass is observed under normal diet and high-fat feeding relative to controls
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:116576)
  • blood glucose is not significantly different from wild-type regardless of diet
  • glucose tolerance does not differ significantly, but there is a trend toward higher 30-minute glucose values in female mutants on both normal and high-fat diets
  • insulin tolerance is similar to wild-type on both normal and high-fat diets
• insulin resistance (MGI Ref ID J:116576)
  • significant insulin resistance is observed in mice fed a high-fat diet
• cellular phenotype
• abnormal apoptosis (MGI Ref ID J:116576)
  • islets are significantly mores susceptible to apoptosis at physiological glucose concentrations, in the presences of palmitate, or in the absence of serum

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Cd38^tm1Lnd/Cd38^tm1Lnd

        involves: 129P2/OlaHsd * C57BL/6J

• immune system phenotype
• abnormal humoral immune response (MGI Ref ID J:49170)
  • impaired antibody response to T cell dependent antigens

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cd38^tm1Lnd related

Cancer Research
Genes Regulating Growth and Proliferation

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Inflammation

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cd38tm1Lnd
Allele Name		targeted mutation 1, Frances E Lund
Allele Type		Targeted (knock-out)
Common Name(s)		CD38-; CD38null;
Mutation Made By		Debra Cockayne,   Roche Bioscience
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Cd38, CD38 antigen
Chromosome		5
Gene Common Name(s)		CD38 antigen, related sequence 1; Cd38-rs1; T10;
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. [MGI Ref ID J:49170]

Genotyping

Genotyping Information

Genotyping Protocols

Cd38^tm1Ldn, STD PCR, vers. 1
NEOTD (Generic Neo), STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Cockayne DA; Muchamuel T; Grimaldi JC; Muller-Steffner H; Randall TD; Lund FE; Murray R; Schuber F; Howard MC. 1998. Mice deficient for the ecto-nicotinamide adenine dinucleotide Blood 92(4):1324-33. [PubMed: 9694721]  [MGI Ref ID J:49170]

Additional References

Kato I; Yamamoto Y; Fujimura M; Noguchi N; Takasawa S; Okamoto H. 1999. CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretion. J Biol Chem 274(4):1869-72. [PubMed: 9890936]  [MGI Ref ID J:52933]

Cd38^tm1Lnd related

Aksoy P; White TA; Thompson M; Chini EN. 2006. Regulation of intracellular levels of NAD: A novel role for CD38. Biochem Biophys Res Commun 345(4):1386-92. [PubMed: 16730329]  [MGI Ref ID J:109655]

Barbosa MT; Soares SM; Novak CM; Sinclair D; Levine JA; Aksoy P; Chini EN. 2007. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. FASEB J 21(13):3629-39. [PubMed: 17585054]  [MGI Ref ID J:134922]

Bergthorsdottir S; Gallagher A; Jainandunsing S; Cockayne D; Sutton J; Leanderson T; Gray D. 2001. Signals that initiate somatic hypermutation of B cells in vitro. J Immunol 166(4):2228-34. [PubMed: 11160276]  [MGI Ref ID J:127146]

Ceni C; Pochon N; Villaz M; Muller-Steffner H; Schuber F; Baratier J; De Waard M; Ronjat M; Moutin MJ. 2006. The CD38-independent ADP-ribosyl cyclase from mouse brain synaptosomes: a comparative study of neonate and adult brain. Biochem J 395(2):417-26. [PubMed: 16411897]  [MGI Ref ID J:115899]

Chen J; Chen YG; Reifsnyder PC; Schott WH; Lee CH; Osborne M; Scheuplein F; Haag F; Koch-Nolte F; Serreze DV; Leiter EH. 2006. Targeted disruption of CD38 accelerates autoimmune diabetes in NOD/Lt mice by enhancing autoimmunity in an ADP-ribosyltransferase 2-dependent fashion. J Immunol 176(8):4590-9. [PubMed: 16585549]  [MGI Ref ID J:108097]

Chen YG; Chen J; Osborne MA; Chapman HD; Besra GS; Porcelli SA; Leiter EH; Wilson SB; Serreze DV. 2006. CD38 is required for the peripheral survival of immunotolerogenic CD4+ invariant NK T cells in nonobese diabetic mice. J Immunol 177(5):2939-47. [PubMed: 16920929]  [MGI Ref ID J:112615]

Deshpande DA; White TA; Guedes AG; Milla C; Walseth TF; Lund FE; Kannan MS. 2005. Altered airway responsiveness in CD38-deficient mice. Am J Respir Cell Mol Biol 32(2):149-56. [PubMed: 15557017]  [MGI Ref ID J:107616]

Gul R; Kim SY; Park KH; Kim BJ; Kim SJ; Im MJ; Kim UH. 2008. A novel signaling pathway of ADP-ribosyl cyclase activation by angiotensin II in adult rat cardiomyocytes. Am J Physiol Heart Circ Physiol 295(1):H77-88. [PubMed: 18456728]  [MGI Ref ID J:138213]

Iqbal J; Zaidi M. 2006. TNF regulates cellular NAD+ metabolism in primary macrophages. Biochem Biophys Res Commun 342(4):1312-8. [PubMed: 16516847]  [MGI Ref ID J:107073]

Johnson JD; Ford EL; Bernal-Mizrachi E; Kusser KL; Luciani DS; Han Z; Tran H; Randall TD; Lund FE; Polonsky KS. 2006. Suppressed insulin signaling and increased apoptosis in CD38-null islets. Diabetes 55(10):2737-46. [PubMed: 17003338]  [MGI Ref ID J:116576]

Krebs C; Adriouch S; Braasch F; Koestner W; Leiter EH; Seman M; Lund FE; Oppenheimer N; Haag F; Koch-Nolte F. 2005. CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins. J Immunol 174(6):3298-305. [PubMed: 15749861]  [MGI Ref ID J:97699]

Manjarrez-Orduno N; Moreno-Garcia ME; Fink K; Santos-Argumedo L. 2007. CD38 cross-linking enhances TLR-induced B cell proliferation but decreases IgM plasma cell differentiation. Eur J Immunol 37(2):358-67. [PubMed: 17274001]  [MGI Ref ID J:117900]

Mayo L; Jacob-Hirsch J; Amariglio N; Rechavi G; Moutin MJ; Lund FE; Stein R. 2008. Dual role of CD38 in microglial activation and activation-induced cell death. J Immunol 181(1):92-103. [PubMed: 18566373]  [MGI Ref ID J:137179]

Partida-Sanchez S; Cockayne DA; Monard S; Jacobson EL; Oppenheimer N; Garvy B; Kusser K; Goodrich S; Howard M; Harmsen A; Randall TD; Lund FE. 2001. Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med 7(11):1209-16. [PubMed: 11689885]  [MGI Ref ID J:126192]

Partida-Sanchez S; Goodrich S; Kusser K; Oppenheimer N; Randall TD; Lund FE. 2004. Regulation of dendritic cell trafficking by the ADP-ribosyl cyclase CD38: impact on the development of humoral immunity. Immunity 20(3):279-91. [PubMed: 15030772]  [MGI Ref ID J:89773]

Rodriguez-Alba JC; Moreno-Garcia ME; Sandoval-Montes C; Rosales-Garcia VH; Santos-Argumedo L. 2008. CD38 induces differentiation of immature transitional 2 B lymphocytes in the spleen. Blood 111(7):3644-52. [PubMed: 18223169]  [MGI Ref ID J:133536]

Shi G; Partida-Sanchez S; Misra RS; Tighe M; Borchers MT; Lee JJ; Simon MI; Lund FE. 2007. Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. J Exp Med 204(11):2705-18. [PubMed: 17938235]  [MGI Ref ID J:126146]

Sun L; Iqbal J; Dolgilevich S; Yuen T; Wu XB; Moonga BS; Adebanjo OA; Bevis PJ; Lund F; Huang CL; Blair HC; Abe E; Zaidi M. 2003. Disordered osteoclast formation and function in a CD38 (ADP-ribosyl cyclase)-deficient mouse establishes an essential role for CD38 in bone resorption. FASEB J 17(3):369-75. [PubMed: 12631576]  [MGI Ref ID J:82191]

Young GS; Choleris E; Lund FE; Kirkland JB. 2006. Decreased cADPR and increased NAD+ in the Cd38-/- mouse. Biochem Biophys Res Commun 346(1):188-92. [PubMed: 16750163]  [MGI Ref ID J:110441]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129P2 background and has been backcrossed to C57BL/6J for twelve generations. Homozygous mice are more susceptible to pathogenic bacteria so conventional specific pathogen-free (SPF) conditions are recommended.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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