ORIGIN
The RIP-HAT rat was created utilizing the RIPHAT transgene consisting 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. The construct was microinjected into fertilized Sprague Dawley eggs to generate the founder rats. Transferred to Charles River for distribution in 2011.
STRAIN CODE
Coming Soon
COAT COLOR
White (Albino)
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
- Develops diabetes between 5-10months of age
- Approximate 60% deficit in β-cell mass due to an increased β-cell apoptosis
- Mean body weight of transgenic mice is approximately 80% of that of wild-type after 5 months
- No difference in mean total pancreas weight between the HIP rat and wild-type at any age
- β-cell mass in transgenic and wild-type animals were comparable until 5 months of age. β-cell mass continued to increase in the wild-type but decreased in the HIP rats until approximately a 60% deficit was reached at the onset of diabetes.
- Histopathology shows an increase in deposit of amyloid in the transgenic rats and frequent β-cell replication and apoptosis with aging when compared to controls.
- Larger size allows physiological measurements.
RESEARCH APPLICATION
Diabetes
ADDITIONAL INFORMATION
For additional information about RIP-HAT rats, please contact us at info@eu.crl.com.
DISCLAIMER
RIP-HAT rats may be subject to the licensed patents and are sold only for research purposes under agreement from Pfizer, Inc.