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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
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Description
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 Mutant Mice. Species laboratory mouse Generation N1F1+N1p (24-JUL-05) Donating 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
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005114 NOD.FVB-Tg(Ins1-Cat,Tyr)25Pne/PneJ
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Tg(Ins1-EGFP/GH1)14Hara/0
NOD/ShiLtJ-Tg(Ins1-EGFP/GH1)14Hara
- lethality-prenatal/perinatal
- *normal* lethality-prenatal/perinatal (MGI Ref ID J:127015)
- reduced litter sizes are observed, with homozygotes being underrepresented; few homozygotes survive to weaning age
- immune system phenotype
- increased susceptibility to autoimmune diabetes (MGI Ref ID J:127015)
- homozygotes surviving past weaning all develop severe insulin-dependent diabetes between 3 and 7 weeks of age
- endocrine/exocrine gland phenotype
- decreased pancreatic beta cell number (MGI Ref ID J:127015)
- a severe paucity of beta cells is observed in diabetic juvenile homozygotes
- digestive/alimentary phenotype
- decreased pancreatic beta cell number (MGI Ref ID J:127015)
- a severe paucity of beta cells is observed in diabetic juvenile homozygotes
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 (MGI Ref ID J:127015)
- 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
- 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
- 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
- insulitis (MGI Ref ID J:127015)
- 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
- in a subset of non-diabetic animals at 30 weeks, some mice show widespread invasive insulitis
- endocrine/exocrine gland phenotype
- abnormal pancreatic beta cell morphology (MGI Ref ID J:127015)
- 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
- insulitis (MGI Ref ID J:127015)
- 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
- in a subset of non-diabetic animals at 30 weeks, some mice show widespread invasive insulitis
- homeostasis/metabolism phenotype
- decreased circulating insulin level (MGI Ref ID J:127015)
- in 30-week old hemizygous males, there is a 2-fold decrease in plasma insulin content compared to non-diabetic NOD/ShiLt controls
- impaired glucose tolerance (MGI Ref ID J:127015)
- 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
- digestive/alimentary phenotype
- abnormal pancreatic beta cell morphology (MGI Ref ID J:127015)
- 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
- insulitis (MGI Ref ID J:127015)
- 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
- in a subset of non-diabetic animals at 30 weeks, some mice show widespread invasive insulitis
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 and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Research Tools
Diabetes and Obesity Research
Fluorescent Proteins
Genetics Research (Tissue/Cell Markers: pancreatic beta cells)
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information
| 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Fluorescent Proteins (Generic GFP), MCA, vers. 2
Fluorescent Proteins (Generic GFP), STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
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
Currently there no information available for this strain. This may be due to the supply level of this strain.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| 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. |
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 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
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