|
Model Characteristics - Model:
LHBETATAG
|
| Model Descriptor |
LHBETATAG
|
| Official Nomenclature |
|
| Genotype |
|
| Species |
Mouse (Mus musculus)
|
| Strain |
Not specified
|
| Is This a Tool Strain? |
No
|
Developmental Stage
(applies only to Zebrafish) |
|
| Experimental Design |
The LHBETATAG retinoblastoma mouse model was developed by Dr. Jolene Windle at the San Antonio Cancer Center and characterized by Drs. Daniel Albert, Joan O’Brien and Dennis Marcus while they were at the Massachusetts Eye and Ear Infirmary. Drs. Windle and Albert have continued in collaboration in the development of alternative transgenic animal models for the evaluation and elucidation of mechanisms of tumorigenesis in ocular retinoblastoma. Use of this animal model has been validated in a number of laboratories with a particular emphasis on histopathology, tumor development and treatment response.
The transgenic retinoblastoma mice are currently maintained at the Bascom Palmer Eye Institute, University of Miami as a colony.
Briefly, The LHBETATAG mouse model is a genetically stable transgenic mouse in which the Simian Virus 40 Large T antigen is expressed from the promoter for the beta-subunit of the human luteinizing hormone. This promoter drives high-level expression of SV40 Large T antigen to the eye, which binds tumor suppressor p105-Rb and p53. Absence of this gene products cause cells to undergo uncontrolled cell division, resulting in bilateral, multi-focal retinal tumors in the animals that become apparent at 4 weeks of age and fill the orbit by 16 weeks of age. These tumors are predictable, reproducible and are microscopically identical to human retinoblastoma forming both Flexner-Wintersteiner and Homer-Wright rosettes. These retinal tumors exhibit antigenic reactivity similar to the human counterpart and like human retinoblastoma, are locally invasive to the choroid, vitreous and optic nerve. Similar to human retinoblastoma these tumors are highly vascularized.
|
| Phenotype |
PURPOSE: To evaluate the effect of subconjunctival injections of combretastatin A-4 phosphate (CA-4P) prodrug treatment on tumor vasculature and growth in an animal model of hereditary retinoblastoma. METHODS: Twenty-four, 12-week-old simian virus-40 T-antigen-positive mice received six subconjunctival CA-4P injections at doses of 0.5, 1.0, 1.5, and 2.0 mg delivered at 72-hour intervals to the right eye only. Six control animals received placebo treatment. All animals underwent serial ophthalmic evaluations and were euthanatized at 16 weeks of age, and eyes were obtained for histopathologic examination. Eyes were graded for presence or absence of tumor, delay of tumor growth, and intratumoral vascularity. RESULTS: The use of subconjunctivally injected CA-4P prodrug induced an extensive, dose-dependent decrease in microvessel density and led to significant tumor reduction in treated eyes compared with the placebo control (P <0.001). No evidence of corneal, lenticular, choroidal, or retinal toxicity was observed by histopathologic evaluation. CONCLUSIONS: Subconjunctival delivery of CA-4P is associated with extensive dose-dependent reduction in blood vessel count in this murine model of retinoblastoma. A combination treatment of retinoblastoma incorporating CA-4P may allow enhanced tumor reduction enabling a decrease in standard treatment doses of both chemotherapy and external beam radiotherapy.
|
| Website for add. info |
|
| Breeding Notes |
|
| Sex Distribution of the Phenotype |
|
| Submitted by |
Murray, Timothy
|
| Principal Investigator / Lab |
Murray, Timothy
|
| Comment |
|
| |
| Model Availability: This model is available from |
| Strain |
Distributor |
Stock number |
|
| |
 Comments (Please login to submit new comments) |
|
