Transgenic Models in Retinoblastoma Research

Abstract

Understanding the mechanism of retinoblastoma (Rb) tumor initiation, development, progression and metastasis in vivo mandates the use of animal models that mimic this intraocular tumor in its genetic, anatomic, histologic and ultrastructural features. An early setback for developing mouse Rb models was that Rb mutations did not cause tumorigenesis in murine retinas. Subsequently, the discovery that the p107 protein takes over the role of pRb in mice led to the development of several animal models that phenotypically and histologically resemble the human form. This paper summarizes the transgenic models that have been developed over the last three decades. . The SV40 genome has several oncogenes in both the large T and the small t region which are predicted to cause a neoplastic transformation of the tissues by binding to p53, the pRB family and phosphatase pp2A proteins [2] . The murine eye tumors showed the histological characteristics of human Rb, including the presence of the neuronal marker NSE and synaptophysin

Kif14 overexpression accelerates murine retinoblastoma development

“…TAg‐RB has a number of advantages over other retinoblastoma mouse models, as it bears strong resemblance to the human tumors. It shares the expression pattern of a number of genes, including Kif14 , with the human disease, and it is the most commonly used model of retinoblastoma for preclinical studies . The tumors initiate in the INL, a possible layer of origin of human tumors, and they contain both Flexner‐Wintersteiner and Homer Wright rosettes, histopathological hallmarks of human retinoblastoma that are not seen together in other mouse models of retinoblastoma …”

A three-dimensional organoid model recapitulates tumorigenic aspects and drug responses of advanced human retinoblastoma

“…Genetically engineered mouse models (GEMMs) are powerful tools to study pathogenesis and develop new therapies for RB 12 , 13 . Unlike in human RB, additional genes must be inactivated together with Rb1 to induce tumorigenesis in mice 13 – 15 .…”

“…Genetically engineered mouse models (GEMMs) are powerful tools to study pathogenesis and develop new therapies for RB 12 , 13 . Unlike in human RB, additional genes must be inactivated together with Rb1 to induce tumorigenesis in mice 13 – 15 . Molecular and cellular analyses indicate that mouse RB has properties of amacrine/horizontal interneurons, reflective of the tumor cells of origin 12 , 14 , 16 .…”

The chick eye in vision research: An excellent model for the study of ocular disease

“…Some of these reviews include Graw (1999) and Marchitti et al (2008) for mutants used in studying cataract and lens development, Graw (2003) for congenital ocular defects, Kao (2006) and Marchitti et al (2008) for corneal disease, Lindsey and Weinreb (2005) for induced mutant glaucoma models, Pang et al (2015) for viral vector-induced glaucoma models, Chakraborty and Pardue (2015) for mutant models used to study refractive development, Baehr and Frederick (2009) for naturally occurring mutant models of outer retinal disease, Dalke and Graw (2005) for natural and induced mutant models for congenital retinal disease, Nair and Vemuganti (2015) for retinoblastoma mutant models, and Yang et al (2008) for uveal melanoma xenograft models. A detailed database of murine mutants and genetic diseases and conditions reported in mice can be found at the Jackson Laboratory Mouse Genome Informatics (MGI) website, http://www.informatics.jax.org/.…”