research animal models

ORIGIN
The RIPHAT transgene consists of a PCR-generated cDNA encompassing the h-IAPP coding sequence under the regulation of the rat insulin II promoter/5’untranslated region and followed by intron I from the human albumin gene and the polyadenylation site/RNA termination region from the human glyceraldehydes-3-phosphate gene. Hemizygotes of the RHF line described in Couce et al. (Pfizer) were self-crossed to generate F1 offspring. Transgenic offspring were identified by PCR amplification of RIPHAT from tail tissue. Transferred to Charles River under exclusive license in 2011.

STRAIN CODE
Coming Soon

COAT COLOR
White

MUTATION INFORMATION
The islet in type 2 diabetes is characterized by a deficit in β-cell mass, increased β-cell apoptosis and impaired insulin secretion. In addition, the islets often contain deposits of islet amyloid, a protein derived from islet amyloid polypeptide (IAPP) that is co-secreted with insulin by β-cells. These proteins can form amyloid tendrils or oligomers which can initiate apoptosis. Animals with high levels of IAPP would be expected to develop diabetes due to the increased presence of the oligomers.

Rats and mice have similar IAPP homology but differ from humans by substitution of proline residues in the amyloidogenic portion of IAPP, and do not form amyloid tendrils or oligomers nor spontaneously develop diabetes in midlife. Thus, insertion of a human transgene, may provide a means to explore the role of oligomers in β-cell destruction.

Features of the Model

• Male homozygous mice spontaneously develop diabetes mellitus by 4-8 weeks of age. Only a subset of female homozygous  mice ( approx 20%) develop diabetes  by 30 weeks.
• Selective β-cell death 
• Impaired insulin secretion
• Plasma insulin concentration is similar in both sexes in transgenic and wild-type animals at 8 weeks of age.  By 16 weeks, in male transgenic animals, plasma insulin concentrations are significantly lower than in control animals, and generally results in death.
• For female transgenic animals at 16 weeks, the plasma insulin concentration was comparable to controls despite the presence of mild hyperglycemia.

RESEARCH APPLICATION
Diabetes

ORDERING INFORMATION
Please call 1.800.LAB.RATS if you would like to place an order.

For additional information about Rip-HAT mice, please contact Technical Services at 1.877.CRIVER.1 (1.877.274.8371) or askcharlesriver@crl.com.

DISCLAIMER
Rip-HAT mice may be subject to the licensed patents and are sold only for research purposes under agreement from Pfizer, Inc.