Mouse Model for Investigation of the Function of the Potentially Cancer Causing Ret Proto-Oncogene

Lead Inventor: Franklin Costantini, Ph.D. Proto-Oncogenes that Produce Cancer Causing Oncogenes Studied In biomedical research, transgenic mouse models are utilized to provide a test subject as a substitute of human test subjects. These mouse models are designed by altering a gene of interest in a mouse's genome to induce or repress genetic expression. This technology has been around since the 1980s, with many significant lines of transgenic and knockout mice being developed every year. However, these mouse models need to be extensively investigated to validate that the desired modeled genotype was produced and the desired phenotype is being expressed. Understanding development and cell lineage are key to combating genetic and developmental diseases. Thus there is a need for new model systems that allow the study of cell lineage. One desired model is for the investigation of the triggers of proto-oncogenes than produce oncogenes. An oncogene is a gene that has the potential to cause cancer because of a mutation that leads to mutant proteins that produce abnormal regulation of cellular growth. Deeper study of these proto-oncogenes will provide insight to the mutations that are benign versus those that may lead to the development of tumors. Line of Transgenic Mice Generated to Aid in Proto-Oncogene Research The lead inventor has generated a line of transgenic mice that aid in researching the role of Ret tyrosine kinase as a proto-oncogene in vivo. This transgenic mouse model expresses a targeted F1072A mutation of the Ret9 tyrosine kinase. This mutation altered the carboxy terminus of the kinase. This mutation results in the removal of the carboxy-terminal PDZ binding motif specific to Ret9. However, homozygous F1072A mice demonstrated no defects in enteric nervous system development, appeared normal in size, morphology, behavior and fertility and no significant deaths were observed. This model offered insight to delimiting the sequences that are important to signaling by the Ret9 isoforms in vivo. Applications: • The study of the proto-oncogene Ret9 and the identification of specific oncogene sequence regions. • The study of mutant Ret expression and its effect on cellular signaling. Advantages: • Developed and validated mouse model for the properties of the Ret9 tyrosine kinase proto-oncogene, easing research time and costs. Patent Status: Copyright Licensing Status: Copyright, Available for Express Licensing & Sponsored Research Support Publications: Costantini et. al. Molecular & Cellular Biology 2005 25 Express Licensing: https://www.flintbox.com/public/project/7712/