Dysautonomia
Foundation Research --
Current Projects
Yang Xu
Construction of Mouse Models for Familial Dysautonomia
Since the
publication of the mutations in IKAP gene in FD patients, we have initiated
research to determine the physiological functions of IKAP and create mouse
models to study the basis of FD pathogenesis. In this context, we are employing
mouse genetics, and particularly the "knock-in" technology, to
introduce site-specific mutations (6TC and R696P) into the endogenous IKAP gene
in mice. Therefore, the mutant IKAP is expressed under its own endogenous
promoter and other regulatory element. A battery of assays will be used to
examine these mice for FD defects. For example, comprehensive histological
analysis of various tissues from 6TC and R696P mice will be performed to
identify any gross defects in various tissues, particularly the central and
peripheral nervous systems. FD patients suffer from the progressive depletion of
sensory and autonomic neurons. Therefore, we will examine the development and
presence of the sensory and autonomic neurons in 6TC, R696P and control
wild-type mice of various developmental stages. This series of experiments
should test whether 6TC and R696P mice recapitulate most of the FD defects and
indicate the usefulness of these mutant mice as mouse models to study the basis
of FD defects. In conclusion, the proposed studies focus on creation and
characterization of mouse models for FD. The successful completion of these
studies could provide foundation for future development of novel therapeutic
methods for FD.
Yang
Xu, Ph. D.
Assistant
Professor of Biology
University of California, San Diego
I received my Ph.D. degree from Harvard University in 1994 and afterwards, conducted three-year postdoctoral research at the Biology Department of MIT. I joined the Biology faculty at University of California, San Diego, in 1997. My research has been focused on establishment of mouse models to study the basis of defects in various human genetic diseases. We have successfully created and characterized a mouse model for Ataxia-telangiectsia (A-T) which is an autosomal recessive human genetic diseases with multiple systemic and cellular defects, including growth retardation, neuronal degeneration, immune defects and high incidence of cancer. We have used this A-T mouse model to elucidate the mechanisms of defects in A-T. In addition, we have recently created a mouse model for an A-T related human genetic disease Nijmegen breakage syndrome. We also employed mouse genetics to establish mouse models for analysis of the regulation of p53 stability and activity.