Retinal pigmentation is one of several factors that profoundly influence visual system development. This is indicated by the fact that albino mammals (including humans), in addition to their external pigmentation deficits, have abnormalities of visual system development. Introduction of a functional tyrosinase gene into albino animals (mice and rabbits) corrects all of these abnormalities, proving that all aspects of this phenotype are due to the single gene defect in tyrosinase. Although it is known that the contribution of tyrosinase is crucial to visual system development, it is not known when or how tyrosinase influences development. I propose to determine the timepoints at which tyrosinase expression is necessary for the prevention of two albino abnormalities: decreased rod cell density, and a disruption of the retinogeniculate pathway through the regulated expression of tyrosinase during critical periods in the development of these two components of the visual system. Insight into the developmental function of tyrosinase will shed light on some fundamental issues of neuronal development, such as cell fate determination, axonal tracking, the timing of neurogenesis, and programmed cell death during development. I will control tyrosinase expression through the creation and use of a novel method of regulating transgenes in mice which involves modification of regulatory elements from the lac operon of E. coli for use in the mammalian genome. Tight regulation over the expression of transgenes will allow the investigation of a variety of previously unanswerable questions, including those addressed in the current proposal. This project will set the groundwork for a substantial broadening of the range of issues that can be addressed with transgenic mouse models.
| Cronin1, Carolyn A; Fortes, Manuel; Lee, Teng C (2014) Position Dependent Carotid Impingement Causing Recurrent Strokes. J Neurol Transl Neurosci 2:1038 |
| Cronin, Carolyn A; Hermann, Lisa D (2014) Right Hemisphere Ischemia is more likely to Cause Falsely ""Mild"" Symptoms and Poor Outcomes without Thrombolysis. J Neurol Transl Neurosci 2: |
