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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Former Names NOD/LtJ-Tg(Ins1-EGFP/GH1)14Hara/HaraJ (Changed: 23-FEB-07 ) NOD/LtJ-Tg(Ins1-EGFP)14Hara/HaraJ (Changed: 05-OCT-05 ) Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N1F1+N1p (24-JUL-05)
Generation DefinitionsDonating Investigator Manami Hara, University of Chicago Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/TyrcImportant Note
The expression of fluorochromes in the beta cells of hemizygous Ins1-EGFP transgenic mice elicit pathophysiological changes which may complicate interpretations if islets from this model are used in transplantation studies. These pathophysiological changes alter the normal pathogenic progression in the NOD mouse model of autoimmune diabetes. Preliminary studies indicate that hemizygous mice are not suitable as recipients of diabetogenic T cells.Description
Donating investigator reports transgenic mice develop normally and behave similarly to controls with respect to glucose tolerence and and pancreatic insulin content. Histology confirms transgenic mice have normal islet architecture with coexpression of insulin and GFP. The enhanced GFP reporter allows the beta cells to be easily identified and purified for further studies.Studies completed at The Jackson Laboratory indicate there is strong non-mosaic expression of green fluorescent protein in NOD/LtJ-Tg(Ins1-EGFP/GH1)14Hara/HaraJ islets. 100% of homozygous Ins1-EGFP transgenic males and females, identified by qPCR, become diabetic by 9 weeks of age. Pancreatic histopathology of homozygous mice shows beta cell loss without insulitis.
Hemizygous Ins1-EGFP mice are viable and are used for breeding. A 30-week incidence study comparing NOD/LtJ controls with mice hemizygous for the Ins1-EGFP transgene shows severely depressed diabetes incidence in these hemizygotes, with males atypically at greater risk than females. Glucose tolerance in prediabetic, Ins1-EGFP transgenic hemizygous 8-week-old males is selectively impaired compared to wild type controls. Although these 8-week-old Ins1-EGFP transgenic and wild type males did not differ in plasma insulin content; a significant decline was noted in hemizygous Ins1-EGFP transgenic males compared to normoglycemic wildtype males when sampled at 30 wk. Adoptive transfer of highly diabetogenic CTL (AI4 TCRTg Rag) CD8+ T cells produced diabetes within 8 days post-injection into NOD/Lt females, but failed to produce any diabetes or even home to islets weeks after injection into hemizygous females. Pancreatic histopathology of 31 week old, non-diabetic, hemizygous Ins1-EGFP transgenic males and females indicate peri and intra islet fibrosis, peri-insulitis and depleted beta cell granulation in 70% of the animals, while only 30% of the mice have intra islet insulitis.
This model provides a valuable tool for studying beta-cell biology, including identification of progenitor cells.
Development
This transgenic allele expresses Enhanced Green Flourescent Protein fused to a 2.1kb fragment of human Growth Hormone under the control of Mouse Insulin Promoter 1. The transgenic construct was injected directly into NOD/LtJ oocytes. Founder 14 was mated to NOD/LtJ. In 2005, The Jackson Laboratory recieved transgenic progeny from the founder, backcrossed once to NOD/LtJ prior to brother-sister mating.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (358 strains)
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018149 FVB/N-Tg(Ins1-GAS)1Sbr/J 005114 NOD.FVB-Tg(Ins1-Cat,Tyr)25Pne/PneJ
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Isolated Growth Hormone Deficiency, Type IA; IGHD1A (GH1)
Isolated Growth Hormone Deficiency, Type IB; IGHD1B (GH1)
Isolated Growth Hormone Deficiency, Type II; IGHD2 (GH1)
Kowarski Syndrome (GH1)
assigned by genotype
Tg(Ins1-EGFP/GH1)14Hara/0
NOD/ShiLtJ-Tg(Ins1-EGFP/GH1)14Hara
- mortality/aging
- *normal* mortality/aging
- reduced litter sizes are observed, with homozygotes being underrepresented; few homozygotes survive to weaning age (MGI Ref ID J:127015)
- immune system phenotype
- increased susceptibility to autoimmune diabetes
- homozygotes surviving past weaning all develop severe insulin-dependent diabetes between 3 and 7 weeks of age (MGI Ref ID J:127015)
- endocrine/exocrine gland phenotype
- decreased pancreatic beta cell number
- a severe paucity of beta cells is observed in diabetic juvenile homozygotes (MGI Ref ID J:127015)
Tg(Ins1-EGFP/GH1)14Hara/Tg(Ins1-EGFP/GH1)14Hara
NOD/ShiLtJ-Tg(Ins1-EGFP/GH1)14Hara
- immune system phenotype
- decreased susceptibility to autoimmune disorder
- development of clinical diabetes is almost completely suppressed in hemizygous females followed to 30 weeks of age, whereas hemizygous males develop a low frequency of clinical diabetes (30-40%) that was comparable to NOD/ShiLtJ control males (MGI Ref ID J:127015)
- cyclophosphamide-injected 8 week old females all developed diabetes within 12 days, but only 2/6 injected transgenic females (at 22 weeks of age) develop disease (MGI Ref ID J:127015)
- when diabetogenic CD8+ T-effector cells from NOD.Cg-Rag1tm1Mom Tg(TcraAI4)1Dvs Tg(TcrbAI4)1Dvs or NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa mice are adoptively transferred to irradiated female NOD/ShiLtJ-Tg(Ins1-EGFP/GH1)14Hara mice and control NOD/ShiLt mice, ~25% of transgenic recipients become diabetic by 11 days post-transfer compared to 5/8 control females (MGI Ref ID J:127015)
- insulitis
- present in pancreata of some but not all non-diabetic hemizygotes at 30 weeks of age; 2/22 males and 3/17 females showed widespread invasive insulitis, while in 13/22 males and 9/17 females, no intra-islet insulitis was observed along with hyperplastic/hypertrophic increases in islet size; remaining males and females showed combination of insulitic and insulitis-free islets (MGI Ref ID J:127015)
- in a subset of non-diabetic animals at 30 weeks, some mice show widespread invasive insulitis (MGI Ref ID J:127015)
- endocrine/exocrine gland phenotype
- abnormal pancreatic beta cell morphology
- many islets of insulitis-free animals and animals displaying a mix of insulitic and normal islets show peri-insular and intra-islet fibrosis, in contrast to NOD/ShiLt controls (MGI Ref ID J:127015)
- insulitis
- present in pancreata of some but not all non-diabetic hemizygotes at 30 weeks of age; 2/22 males and 3/17 females showed widespread invasive insulitis, while in 13/22 males and 9/17 females, no intra-islet insulitis was observed along with hyperplastic/hypertrophic increases in islet size; remaining males and females showed combination of insulitic and insulitis-free islets (MGI Ref ID J:127015)
- in a subset of non-diabetic animals at 30 weeks, some mice show widespread invasive insulitis (MGI Ref ID J:127015)
- homeostasis/metabolism phenotype
- decreased circulating insulin level
- in 30-week old hemizygous males, there is a 2-fold decrease in plasma insulin content compared to non-diabetic NOD/ShiLt controls (MGI Ref ID J:127015)
- impaired glucose tolerance
- impaired glucose tolerance is observed at 8 weeks in hemizygotes in comparison to NOD/ShiLt controls; at 28 weeks, impairment is significantly greater than at 8 weeks (MGI Ref ID J:127015)
This mouse can be used to support research in many areas including:
GFP relatedDiabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains
NOD Transgenics
Immunology, Inflammation and Autoimmunity Research
Autoimmunity
Type 1 Diabetes
Research Tools
Diabetes and Obesity Research
Fluorescent Proteins
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: pancreatic beta cells
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Ins1-EGFP/GH1)14Hara | ||
|---|---|---|---|
| Allele Name | transgene insertion 14, Manami Hara | ||
| Allele Type | Transgenic (Reporter) | ||
| Common Name(s) | MIP-GFP; NOD-MIP-GFP; | ||
| Mutation Made By | Manami Hara, University of Chicago | ||
| Strain of Origin | NOD/ShiLtJ | ||
| Site of Expression | Pancreatic islets | ||
| Expressed Gene | GH1, growth hormone 1, human | ||
| Expressed Gene | GFP, Green Fluorescent Protein, jellyfish | ||
| Green Fluorescent Protein (GFP), derived from the jellyfish Aequorea victoria, is a versatile reporter molecule which has found use in many biological applications. In some constructs the original molecule has been modified in order to enhance its fluorescence intensity (EGFP, enhanced GFP). When utilized in a transgenic construct, tissue expressing sufficient amounts of GFP will fluoresce when exposed to a 488 nm light source. | |||
| Promoter | Ins1, insulin 1, rat | ||
| General Note | Transgenic mice develop normally and exhibit glucose tolerance and pancreatic insulin levels similar to those of controls. Histological analysis reveals normal islet architecture and coexpression of insulin and EGFP (J:100005) | ||
| Molecular Note | The transgene comprises a DNA fragment containing the mouse insulin 1 promoter, extending from 8.5 kb upstream of the transcription initiation site to nucleotide +12, driving expression of a fusion gene joining the 7.6-kb coding region of the enhanced green fluorescent protein (EGFP) gene to a 2.1-kb fragment of the human growth hormone 1 gene that confers high-level expression. [MGI Ref ID J:99450] | ||
| Gene Symbol and Name | Tg(Ins1-EGFP/GH1)14Hara, transgene insertion 14, Manami Hara | ||
| Chromosome | UN | ||
| Gene Common Name(s) | MIP-GFP; NOD-MIP-GFP; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Fluorescent Proteins (Generic GFP), Melt Curve Analysis
Fluorescent Proteins (Generic GFP), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Leiter EH; Reifsnyder P; Driver J; Kamdar S; Choisy-Rossi C; Serreze DV; Hara M; Chervonsky A. 2007. Unexpected functional consequences of xenogeneic transgene expression in beta-cells of NOD mice. Diabetes Obes Metab 9 Suppl 2:14-22. [PubMed: 17919174] [MGI Ref ID J:127015]
Additional References
Tg(Ins1-EGFP/GH1)14Hara relatedChong AS; Shen J; Tao J; Yin D; Kuznetsov A; Hara M; Philipson LH. 2006. Reversal of diabetes in non-obese diabetic mice without spleen cell-derived beta cell regeneration. Science 311(5768):1774-5. [PubMed: 16556844] [MGI Ref ID J:107041]
Hara M. 2005. NOD transgenic mice with green fluorescent protein-labeled pancreatic beta cells MGI Direct Data Submission :. [MGI Ref ID J:100005]
Hara M; Wang X; Kawamura T; Bindokas VP; Dizon RF; Alcoser SY; Magnuson MA; Bell GI. 2003. Transgenic mice with green fluorescent protein-labeled pancreatic beta -cells. Am J Physiol Endocrinol Metab 284(1):E177-83. [PubMed: 12388130] [MGI Ref ID J:99450]
Kojima H; Fujimiya M; Matsumura K; Nakahara T; Hara M; Chan L. 2004. Extrapancreatic insulin-producing cells in multiple organs in diabetes. Proc Natl Acad Sci U S A 101(8):2458-63. [PubMed: 14983031] [MGI Ref ID J:107040]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2450.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Embryos
Price (US dollars $) Frozen Embryo $1600.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.Cryorecovery - Standard.
Progeny testing is not required.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3185.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Embryos
Price (US dollars $) Frozen Embryo $2080.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.Cryorecovery - Standard.
Progeny testing is not required.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- 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 | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Important Note
The expression of fluorochromes in the beta cells of hemizygous Ins1-EGFP transgenic mice elicit pathophysiological changes which may complicate interpretations if islets from this model are used in transplantation studies. These pathophysiological changes alter the normal pathogenic progression in the NOD mouse model of autoimmune diabetes. Preliminary studies indicate that hemizygous mice are not suitable as recipients of diabetogenic T cells.
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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.Ordering Information
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For Licensing and Use Restrictions view the link(s) below:
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JAX® Mice, Products & Services Conditions of Use
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