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Strain Name:

FVB/N-Tg(Ins2-IAPP)RHFSoel/J

Stock Number:

008232

Availability:

Under Development for Distribution Colony

To register your interest in this strain go to the Strain Interest Form.

General Terms and Conditions

Genes & Alleles   IAPP;   Ins2;   Tg(Ins2-IAPP)RHFSoel;


Product Information

Strain Details

Type JAX® GEMM® Strain - Coisogenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Donating Investigator Walter Soeller,   Pfizer Inc
GenerationN10+ (22-JUL-08)

Strain Description
Mice homozygous for the RIPHAT transgene are viable and fertile, with expression of human islet amyloid polypeptide (h-IAPP) under the regulatory control of the rat insulin II promoter. While h-IAPP RNA from the transgene is observed in pancreas, kidney, and stomach, h-IAPP protein is reported only in pancreas tissues. Hemizygous mice show no symptoms of spontaneous disease. Homozygous males spontaneously develop diabetes mellitus due to beta-cell death, associated with impaired insulin secretion (hypoinsulinemia), hyperglycemia, and abnormal intracellular aggregates of h-IAPP (the donating investigator reports that extracellular aggregates are not found on this strain background). Homozygous male onset is between 4-8 weeks of age with death around 16 weeks of age. Homozygous females exhibit a less severe phenotype. These RIPHAT transgenic mice may be useful in studying the beta-cell destruction and islet amyloid deposition associated with non-insulin-dependent diabetes mellitus (NIDDM) or Type II diabetes, as well as beta-cell apoptosis and characteristics of the endoplasmic reticulum (ER) stress pathway.

Strain Development
The 2395 bp RIPHAT transgene was designed with (from 5' to 3') the rat insulin II promoter/5' untranslated region, a PCR-generated 270 bp cDNA encompassing the human islet amyloid polypeptide (h-IAPP) coding sequence, 728 bp from the human albumin gene introns 1, and the 525 bp polyadenylylation site/RNA termination region from the human glyceraldehyde-3-phosphate gene (GAPDH). This transgene was microinjected into the pronuclei of FVB/N fertilized oocytes. Mice from the founder line with the highest expression levels in the pancreas (founder line RHF) were established. These mice were maintained by breeding transgenic mice to one another and to FVB/N inbred mice for many generations prior to sending to The Jackson Laboratory. The donating investigator reports that high resolution mapping of the transgene in prometaphase spreads of endoreduplicated cells indicates the transgene insertion at a single location on chromosome 15 (15C); copy number is not known.

Mammalian Phenotype Terms assigned by genotype

Tg(Ins2-IAPP)RHFSoel/Tg(Ins2-IAPP)RHFSoel

        involves: FVB/N
  • homeostasis/metabolism phenotype
  • decreased circulating insulin level (MGI Ref ID J:130022)
  • hyperglycemia (MGI Ref ID J:130022)
  • endocrine/exocrine gland phenotype
  • abnormal islet of Langerhans morphology (MGI Ref ID J:130022)
    • islet cells exhibit an increased expression of the endoplasmic reticulum (ER) chaperon Hspa5 and ER stress markers
    • decreased pancreatic beta cell number (MGI Ref ID J:130022)
      • at 10 weeks, beta cell mass is decreased 48% compared to in wild type mice due to a 6-fold increase in beta cell apoptosis
  • decreased insulin secretion (MGI Ref ID J:130022)
    • despite hyperglycemia, mice exhibit decreased plasma insulin levels compared to Tg(Iapp-Iapp)3Wcs homozygotes implying defective insulin secretion
  • immune system phenotype
  • increased susceptibility to autoimmune diabetes (MGI Ref ID J:130022)
    • mice develop diabetes at 10 weeks of age
  • digestive/alimentary phenotype
  • abnormal islet of Langerhans morphology (MGI Ref ID J:130022)
    • islet cells exhibit an increased expression of the endoplasmic reticulum (ER) chaperon Hspa5 and ER stress markers
    • decreased pancreatic beta cell number (MGI Ref ID J:130022)
      • at 10 weeks, beta cell mass is decreased 48% compared to in wild type mice due to a 6-fold increase in beta cell apoptosis
  • decreased insulin secretion (MGI Ref ID J:130022)
    • despite hyperglycemia, mice exhibit decreased plasma insulin levels compared to Tg(Iapp-Iapp)3Wcs homozygotes implying defective insulin secretion

Gene & Allele Details

Allele Symbol Tg(Ins2-IAPP)RHFSoel
Allele Name transgene insertion RHF, Walter C Soeller
Common Name(s) RIPHAT; RIPHAT line RHF; Tg(IAPP)6Jdm;
Mutation Made By Walter Soeller,   Pfizer Inc
Strain of OriginFVB/N
Expressed Gene IAPP, islet amyloid polypeptide, human
Promoter Ins2, insulin 2, rat
Molecular Note The transgene consisted of cDNA encompassing the Human IAPP coding sequence under the regulation of the rat insulin II promoter (Ins2). [MGI Ref ID J:73886]

Control Information

  Control
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(Ins2-IAPP)RHFSoel

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred. Homozygous males exhibit onset of diabetes mellitus between 4-8 weeks of age with death around 16 weeks of age. Homozygous females exhibit a less severe phenotype.
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of Ins2
005534   B10.Cg-H2d Tg(Ins2-HA)165Bri/ShrmJ
005500   B6.C-Tg(Ins2-GP)34-20Olds/MvhJ
005715   B6.Cg H2g7-Tg(Ins2-CD80)3B7Flv/LwnJ
004826   B6.Cg-Tg(Ins2-NP)25-3Olds/MhvJ
003573   B6.Cg-Tg(Ins2-cre)25Mgn/J
005713   C.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
005533   C.Cg-Tg(Ins2-HA)165Bri/ShrmJ
004827   C.Cg-Tg(Ins2-NP)25-3Olds/MvhJ
005432   C57BL/6-Tg(Ins2-OVA)307Wehi/WehiJ
005433   C57BL/6-Tg(Ins2-OVA)59Wehi/WehiJ
005431   C57BL/6-Tg(Ins2-TFRC/OVA)296Wehi/WehiJ
005564   FVB(Cg)-Tg(Ins2-CALM1)26Ove Tg(Cryaa-TAg)1Ove/PneJ
005522   NOD-Tg(Ins2*Y16A)1Ell/GseJ
005523   NOD-Tg(Ins2*Y16A)3Ell/GseJ
003499   NOD-Tg(Ins2-Fasl)24Ach
007840   NOD.Cg-Prkdcscid Tg(Ins2-CD86)12B70Flv/FswJ
004346   NOD.Cg-Prkdcscid Tg(Ins2-CD80)3B7Flv/DvsJ
004230   NOD.Cg-Prkdcscid Tg(Ins2-E3)1Dvs/DvsJ
003843   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ
003844   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ
005524   NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ
005525   NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1tm1Jja Ins2tm1Jja/GseJ
006254   NOD.Cg-Tg(Ins2-Ccl21b)2Cys/JbsJ
006154   NOD.Cg-Tg(Ins2-Cxcl13)1Cys/JbsJ
003869   NOD.Cg-Tg(Ins2-E3)1Dvs/DvsJ
005685   NOD.Cg-Tg(Ins2-HA)165Bri/ShrmJ
002380   NOD.Cg-Tg(Ins2-TAg)1Lt Prkdcscid/DvsJ
004602   NOD.Cg-Tg(Ins2-rtTA)2Doi/DoiJ
004937   NOD.Cg-Tg(Ins2-tTA)1Doi/DoiJ
005734   NOD/Lt-Tg(Ins2-rtTA)1Ach/AchJ
005870   NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J
006777   NOD/ShiLt-Tg(Ins2-Cd274)2Mdos/MdosJ
005733   NOD/ShiLt-Tg(Ins2-Fas*I246N)1Ach/AchJ
003074   NOD/ShiLt-Tg(Ins2-GAD2)1Lt/LtJ
004986   NOD/ShiLt-Tg(Ins2-cre)3Lt/Lt
003855   NOD/ShiLt-Tg(Ins2-cre)5Lt/LtJ
004987   NOD/ShiLt-Tg(Ins2-cre)6Lt/Lt
002033   NOD/ShiLt-Tg(RipTAg)1Lt/J
004990   NOD/ShiLtDvs-Tg(Ins2-E3*734)4Dvs/DvsJ
005714   NOR.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
008122   STOCK Tg(Ins2-cre/Esr1)1Dam/J
008250   STOCK Tg(Ins2-rtTA)2Efr/J
View Strains carrying other alleles of Ins2     (42 strains)

Additional Web Information

Congenic Nomenclature

Research Applications

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

Apoptosis Research
Endogenous Regulators

Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Insulin Resistance
Type 2 Diabetes (NIDDM)

Mouse/Human Gene Homologs
diabetes mellitus, insulin-resistant

Research Tools
Apoptosis Research
Diabetes and Obesity Research

References

Selected Reference(s)

Couce M; Kane LA; O'Brien TD; Charlesworth J; Soeller W; McNeish J; Kreutter D; Roche P; Butler PC. 1996. Treatment with growth hormone and dexamethasone in mice transgenic for human islet amyloid polypeptide causes islet amyloidosis and beta-cell dysfunction. Diabetes 45(8):1094-101. [PubMed: 8690157]  [MGI Ref ID J:73886]

Janson J; Soeller WC; Roche PC; Nelson RT; Torchia AJ; Kreutter DK; Butler PC. 1996. Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proc Natl Acad Sci U S A 93(14):7283-8. [PubMed: 8692984]  [MGI Ref ID J:47215]

Additional References

Price and Supply Information

Strain Name: FVB/N-Tg(Ins2-IAPP)RHFSoel/J
Stock Number: 008232
 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date: 29-SEP-08

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development

Supply Details

Standard SupplyUnder Development for Distribution Colony
Supply Notes This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

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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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