Disease Models

• Tp53-oncology and carcinogenicity
• Mc4r-obesity and diabetes
• Bcrp- ADME and toxicology
• Trpc4-pain and cardiac defects
• Myo9a-hydrocephalus

Featured Models Tp53-Oncology and Carcinogenicity, Mc4r-Obesity and Diabetes, Pde4d- Inflammation, Bcrp- ADME and Toxicology, Trpc4-Pain and cardiac defects, Myo9a-hydrocephalus.

Mc4r TGEM® (a.k.a. the FatRat™):                

• Mutations in the Mc4r gene in the melanocortin system are the most common cause of monogenic obesity in humans. Therefore, the FatRat™ ideal for obesity research.
• -" The FatRatTM is an obesity rat model with hyperphagia, hyperinsulinemia and elevated leptin.

Obesity phenotype in the Mc4r TGEM® Knockout Rat: Wild type (WT) rat. Mc4r+/- heterozygous rat. Mc4r-/- homozygous rat.

p53 TGEM® Knockout Rat Model                 

• -p53 is the gene most commonly mutated in many human cancers. Therefore, this rat model can be used as an oncology, carcinogenicity, and toxicology research model.
• -The model displays spontaneous tumor formation at 4 months in homozygotes and at 8 months in heterozygotes.

Tumorigenesis in the p53 TGEM® Knockout Rat (A) Macroscopic view of a primary tumor. (B) Macroscopic view of metastases in lungs. (C) Microscopic view of a lung metastasis, H&E stained. (D) Microscopic view of a lung metastasis stained for Factor VIIIa

Bcrp TGEM® Knockout Rat Model                

• -Bcrp is an important drug transport and drug resistance gene that regulates the bioavailability of many drugs and other compounds.
• -" The Bcrp protein is important for drug transport across the blood-brain barrier.

Trpc4 TKO® Knockout Rat Model                

• -This model represents the world's only Transient receptor potential (Trp) knockout rat
• -Trpc4 is associated with pain pathways and its disruption in humans results in cardiovascular defects.
• -The rat model can be used as a pain research model for neuropathic pain and visceral pain.

Trpc4 expression in p5 rat whole body sagittal sections: A) Wild type (WT) rat. Antisense (as) hybridization x-ray film autoradiography shown under dark field illumination. Moderate level mRNA labeling is evident in the brain cortex (Cx) and hippocampus (Hi). Nonspecific lableing is seen in the eye choroids (*) and aorta (**). B) Heterozygous rat (Het). Low to moderate levels of Trpc4 mRNA labeling in the brain cortex and hippocampus. C) Homozygous rat (Hom). Undetectable Trpc4 mRNA levels in the cortex and hippocampus.

Myo9a TKO® Knockout Rat Model                

• -This is the world's only knockout hydrocephalus rat model.
• -The larger size makes this rat model ideal for hydrocephalus research and hydrocephalus shunt implantation.

Hydrocephalus in the Myo9a TKO® Knockout Rat brain: (A , B) Cresyl Violet stained sections of rostral frontal cortex of brains from 6 week old wild type (A) and Myo9a KO rats (B). Note the marked swelling of the lateral ventricles (LV) in the KO. Bar: 100 um.(C , D) Cerebral aqueduct of WT (C) and KO (D) brain. Cortical layers (1-6) and white matter (WM) are present but highly compressed in the KO. Note the severe stenosis of the aqueduct in the KO.(E,F). GFAP immunostaining of sections of the CA1 region of the hippocampus of Myo9b heterozygote (E) and KO (F) littermates at 6 weeks. Note the elevated levels of GFAP expression and increased process branching in the KO astrocytes.