Description

Strain Information

Former Names NOD/Lt-Tg(H2-Ead)5Lt/J    (Changed: 23-FEB-07 ) Type Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse H2 Haplotype g7 Generation F?+8p   Donating Investigator Edward Leiter,   The Jackson Laboratory

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

Description
A requirement for developing insulin-dependent diabetes mellitus (IDDM) in mice is the absence of functional H2-Ea and H2-Ab1 genes. NOD/Lt mice (H2^g7 = K^d, A^g7, E^null, D^b) fulfill this requirement and develop IDDM. Two homozygous transgenic lines (NOD/ShiLt-Tg(H2-Ea^d)5Lt/J (Stock No. 002034) commonly referred to as line 5; and NOD/ShiLt-Tg(H2-Ea^d)12Lt/J (Stock No. 002035), referred to as line 12) were created to further examine the quantitative thresholds of MHC class II expression and the mechanisms involved in preventing IDDM development in NOD mice. These strains harbor a construct containing a complete H2-Ea^d gene from BALB/cByJ mice. Only a single copy of the Ea^d transgene integrated into the genome of line 12 where as four copies are present in line 5. Diabetes incidence in line 12 is greatly reduced (25% of females, 0% of males) where H2-Ea expression on antigen presenting cells is comparable to BALB/cByJ controls. Overexpression of H2-Ea in line 5 confers nearly complete resistance to IDDM. Although the presence of the Ea^d transgene in both lines confers protective influence from IDDM pathologies that affect pancreatic beta cells, autoimmune pathologies effecting other tissues (submandibular salivary, thyroid, kidney) are observed. Histologic examination of thepancreas reveals perivascular/periductal infiltration and peri-insulitus.

Development
A 14 kb XhoI-SacII fragment containing the H2-Ea gene and flanking sequences was isolated from a cosmid of BALB/c origin and utilized in a transgenic construct. The construct was injected into NOD/Lt zygotes. Two founder lines resulted (Stock Nos. 002034 and 002035).

Control Information

	Control
	001976 NOD/ShiLtJ
		Additional control strains are available depending on the researchers needs. Please refer to JAX Notes No. 477 for a complete list of control strains available for NOD/ShiLtJ mice in diabetes research.
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of H2-Ea

005739	NOD-Tg(H2-Ea-Ins2)1Wehi/WehiJ
002035	NOD/ShiLt-Tg(H2-Ead)12Lt/J
001658	STOCK Tg(H2-Ea)16Dim/J
001901	STOCK Tg(H2-Ea*deltaX)16Dim/J
001812	STOCK Tg(H2-Ea*deltaY)54Dim/J

View Strains carrying other alleles of H2-Ea     (5 strains)

Additional Web Information

JAX^® NOTES, Spring 1999; 477. Control Strains for NOD/LtJ Mice in Diabetes Research.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

NOT	Diabetes Mellitus, Insulin-Dependent; IDDM - No similarity to the expected human disease phenotype was found.4

4 One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of those genes, but the phenotype did not resemble the disease.

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(H2-Ea^d)5Lt/0

        NOD/ShiLt-Tg(H2-Ea^d)5Lt

• immune system phenotype
• autoimmune response (MGI Ref ID J:36435)
  • transgenic mice develop autoimmune pathologies against salivary gland, thyroid and kidney comparable to conrol NOD mice, but no islet-directed autoimmune response is observed
• decreased susceptibility to autoimmune diabetes (MGI Ref ID J:36435)
  • no males or females develop diabetes (blood glucose >300 mg/dl) during the 40 week evaluation period compared to 60% and 90% incidence in non-transgenic NOD male and female controls respectively
  • transgenic mice are almost completely resistant to cyclophosphamide-accelerated diabetes unlike NOD controls
• decreased interferon-gamma secretion (MGI Ref ID J:36435)
  • GAD65-reactive T cells from transgenic mice produce significantly lower levels of IFNG than those from NOD controls
• increased interleukin-4 secretion (MGI Ref ID J:36435)
  • IL-4 levels produced by GAD65 responsive T cells of transgenic mice are 9-fold higher compared to NOD controls
• periinsulitis (MGI Ref ID J:36435)
  • pancreata of males and female show peri-insulitis
• endocrine/exocrine gland phenotype
• periinsulitis (MGI Ref ID J:36435)
  • pancreata of males and female show peri-insulitis
• digestive/alimentary phenotype
• periinsulitis (MGI Ref ID J:36435)
  • pancreata of males and female show peri-insulitis

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)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(H2-Ead)5Lt
Allele Name		transgene insertion 5, Edward H Leiter
Allele Type		Transgenic (random, expressed)
Common Name(s)		Tg(Ead)Lt;
Strain of Origin		NOD/ShiLt
Expressed Gene		H2-Ea, histocompatibility 2, class II antigen E alpha, mouse, laboratory
Promoter		H2-Ea, histocompatibility 2, class II antigen E alpha, mouse, laboratory
General Note		Overexpression of H2-Ea in line 5 confers nearly complete resistance to IDDM. Although the presence of the transgene in both lines 5 and 12 confers protective influence from IDDM pathologies that affect pancreatic beta cells, autoimmune pathologies effecting other tissues (submandibular salivary, thyroid, kidney) are observed. Histologic examination of the pancreas reveals perivascular/periductal infiltration and peri-insulitus.
Molecular Note		The construct contains a complete H2-Ead gene from the BALB/cByJ mouse including flanking sequence. One copy of the transgene integrated into the genome of line 12 whereas four copies are present in line 5. [MGI Ref ID J:36435]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Hanson MS; Cetkovic-Cvrlje M; Ramiya VK; Atkinson MA; Maclaren NK; Singh B; Elliott JF; Serreze DV; Leiter EH. 1996. Quantitative thresholds of MHC class II I-E expressed on hemopoietically derived antigen-presenting cells in transgenic NOD/Lt mice determine level of diabetes resistance and indicate mechanism of protection. J Immunol 157(3):1279-87. [PubMed: 8757636]  [MGI Ref ID J:36435]

Additional References

Tg(H2-Ea^d)5Lt related

Leiter EH. 1998. NOD Mice and Related Strains: Origins, Husbandry and Biology Introduction. In: NOD Mice and Related Strains: Research Applications in Diabetes, AIDS, Cancer, and Other Diseases. RG Landes, Austin.  [MGI Ref ID J:110093]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain is maintained by homozygous sibling matings. There have been no reproductive performance problems reported. Expected coat color from breeding:albino

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 Type 1 Diabetes Repository collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	001976 NOD/ShiLtJ
		Additional control strains are available depending on the researchers needs. Please refer to JAX Notes No. 477 for a complete list of control strains available for NOD/ShiLtJ mice in diabetes research.
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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General Terms and Conditions

Contact information

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