NAF Ataxia Research Studies Currently Underway

Sokal V Todi, PhD

The University of Iowa
Generating a conditional knockout mouse to investigate the functional necessity of MJD1, the causative gene for Spinocerebellar Ataxia 3, in mammals

Spinocerebellar Ataxia 3 (SCA3), also know n as Machado-Joseph Disease (MJD), is the most common dominantly inherited ataxia. SCA3/MJD arises from the expansion of a region of the protein ataxin-3 from 12-41 to over 60 repeats of the amino acid glutamate. SCA3/MJD affects nervous system areas such as the basal ganglia, brainstem, cerebellum and the spinal cord.

Not much is known about ataxin-3 functions in an organism. Studies conducted thus far have only shed light onto ataxin-3 interactions with other proteins and some of its enzymatic properties. As a matter of fact, we do not even know if ataxin-3 is an essential protein in mammals.

Research indicates that a considerable number of genes in our genome are not functionally necessary. In this proposal, we will investigate if MJD1, the gene which produces ataxin-3, is necessary for proper functioning of mammals. We aim to generate a mouse model where MJD1 is removed from the animal's genome, to understand functional necessities of ataxin-3 in otherwise normal animals. The information gathered will be important in answering crucial questions, such as: Is ataxin-3 functionally necessary during development or in the adult mammal; What are some possible functions it plays in the nervous system and other organ systems; Can therapeutic techniques, which w ill properly combat deleterious effects of SCA3/MJD, be successfully designed and safely implemented?