Description

Strain Information

Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain NOD/ShiLt Donor Strain C57BL/6   Donating Investigator David Serreze,   The Jackson Laboratory

Appearance
albino, pink eyed
Related Genotype: A/A Tyr^c/Tyr^c

Description
Homozygous mice carrying the (HLA-A2.1)1Enge transgene ubiquitously express significant quantities of the human MHC class I HLA-A2.1 molecules. These HLA-A2.1 molecules mediate beta cell auto-reactive CD8 T cell responses that when added to those elicited by endogenous murine MHC class I variants results in a significantly accelerated rate of diabetes onset in either the hemizygote or homozygote transgenic mouse when compared to NOD/Lt controls (Marron et al., 2002).

This model is useful for studying the role of MHC class I molecules in Type 1 Diabetes.

Development
Using marker assisted analysis for all known Idd loci, the transgenic allele HLA-A2.1 from C57BL/6-Tg(HLA-A2.1)1Enge/J (stock# 3088) was backcrossed10 generations to NOD/Lt prior to making homozygote (Marron et al., 2002). In 2005, the Type 1 Diabetes Resource received NOD.B6-Tg(HLA-A2.1)1Enge/Dvs at N10F34.

Control Information

	Control
	001976 NOD/ShiLtJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(HLA-A2.1)1Enge allele

003475	C57BL/6-Tg(HLA-A2.1)1Enge/J
004548	NOD.Cg-B2mtm1Unc Tg(B2M)55Hpl Tg(HLA-A2.1)1Enge/DvsJ
006609	NOD.Cg-Prkdcscid Tg(HLA-A2.1)1Enge/DvsJ
004262	NOD.Cg-Prkdcscid Tg(HLA-A2.1)1Enge/Dvs

View Strains carrying   Tg(HLA-A2.1)1Enge     (4 strains)

Strains carrying other alleles of HLA-A

004191	B6.Cg-Tg(HLA-A/H2-D)2Enge/J
006611	NOD.129P2(B6)-B2mtm1Unc Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ
006605	NOD.Cg-Prkdcscid Emv30b Tg(HLA-A/H2-D/B2M)1Dvs/DvsJ
005853	NOD.Cg-Tg(HLA-A2/H2-K)1Scr/ShrmJ
006604	NOD/ShiLtDvs-Tg(HLA-A/H2-D/B2M)1Dvs/J

View Strains carrying other alleles of HLA-A     (5 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(HLA-A2.1)1Enge/Tg(HLA-A2.1)1Enge

        NOD.B6-Tg(HLA-A2.1)1Enge

• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:109851)
  • proportions of splenic B cells, CD4, and CD8 T cells are comparable to controls; no differences in CD4+CD25+ T cell numbers or expression levels of endogenous murine MHC class I molecules are found
• increased susceptibility to autoimmune diabetes (MGI Ref ID J:109851)
  • homozygous and heterozygous mice develop type I diabetes at a significantly accelerated rate compared to NOD controls

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)

HLA-A related

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

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(HLA-A2.1)1Enge
Allele Name		transgene insertion 1, Victor H Engelhard
Allele Type		Transgenic (random, expressed)
Mutation Made By		Ai-Xuan Le,   Stanford University
Strain of Origin		C57BL/6
Expressed Gene		HLA-A, major histocompatibility complex, class I, A, human
General Note		Expression of this human class I molecule in transgenic mice does not result in expansion of the number of cytotoxic T lymphocyte (CTL) precursors specific for other human class I Ag, HLA-B27 or HLA-A2.2.
Molecular Note		The transgene contains the full length HLA-A2.1 gene. Expression of human class I MHC Ag HLA-A2.1 was detected on cells from homozygous transgenic spleen, bone marrow, and thymus. [MGI Ref ID J:52612]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(HLA-A2.1)1Enge, QPCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Marron MP; Graser RT; Chapman HD; Serreze DV. 2002. Functional evidence for the mediation of diabetogenic T cell responses by HLA-A2.1 MHC class I molecules through transgenic expression in NOD mice. Proc Natl Acad Sci U S A 99(21):13753-8. [PubMed: 12361980]  [MGI Ref ID J:109851]

Additional References

Tg(HLA-A2.1)1Enge related

Banuelos SJ; Shultz LD; Greiner DL; Burzenski LM; Gott B; Lyons BL; Rossini AA; Appel MC. 2004. Rejection of human islets and human HLA-A2.1 transgenic mouse islets by alloreactive human lymphocytes in immunodeficient NOD-scid and NOD-Rag1(null)Prf1(null) mice. Clin Immunol 112(3):273-83. [PubMed: 15308121]  [MGI Ref ID J:91764]

Le AX; Bernhard EJ; Holterman MJ; Strub S; Parham P; Lacy E; Engelhard VH. 1989. Cytotoxic T cell responses in HLA-A2.1 transgenic mice. Recognition of HLA alloantigens and utilization of HLA-A2.1 as a restriction element. J Immunol 142(4):1366-71. [PubMed: 2464645]  [MGI Ref ID J:52612]

Newberg MH; Smith DH; Haertel SB; Vining DR; Lacy E; Engelhard VH. 1996. Importance of MHC class 1 alpha2 and alpha3 domains in the recognition of self and non-self MHC molecules. J Immunol 156(7):2473-80. [PubMed: 8786307]  [MGI Ref ID J:31937]

Yang J; Qian J; Wezeman M; Wang S; Lin P; Wang M; Yaccoby S; Kwak LW; Barlogie B; Yi Q. 2006. Targeting beta2-microglobulin for induction of tumor apoptosis in human hematological malignancies. Cancer Cell 10(4):295-307. [PubMed: 17045207]  [MGI Ref ID J:114975]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	A footpad injection of Complete Freund s Adjuvant (CFA) administered once at weaning will delay diabetes onset, thus extending the lifespan of breeders. Use of Complete Freund s Adjuvant in NOD mice can be found in Current Protocols in Immunology page 15.9.19, Reproduction.
Diet Information	LabDiet® 5K52/5K67

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

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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 Type 1 Diabetes Repository collection.

Control Information

	Control
	001976 NOD/ShiLtJ
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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

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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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.