A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse.

Journal article

The robotic mouse is an autosomal dominant mutant that arose from a large-scale chemical mutagenesis program. It has a jerky, ataxic gait and develops adult-onset Purkinje cell loss in the cerebellum in a striking region-specific pattern, as well as cataracts. Genetic and physical mapping of the disease locus led to the identification of a missense mutation in a highly conserved region of Af4, a putative transcription factor that has been previously implicated in leukemogenesis. We demonstrate that Af4 is specifically expressed in Purkinje cells, and we hypothesize that the expression of mutant Af4 leads to neurodegeneration. This function was not identified through knock-out studies, highlighting the power of phenotype-driven mutagenesis in the mouse to identify new pathways involved in neurological disease.

Authors: Isaacs, A; Oliver, P; Jones, E; Jeans, A; Potter, A

• Publication status: Published
• Journal: Journal of neuroscience : the official journal of the Society for Neuroscience
• Volume: 23
• Issue: 5
• Pages: 1631-1637
• Publication date: 2003-03-01
• EISSN: 1529-2401
• ISSN: 0270-6474
• Language: English
• Keywords: Thymus Gland; Cell Count; Point Mutation; Cerebellum; Nuclear Proteins; DNA-Binding Proteins; Sequence Homology, Amino Acid; Mice, Neurologic Mutants; Mice; Organ Specificity; Molecular Sequence Data; Purkinje Cells; Cataract; Disease Progression; Physical Chromosome Mapping; Disease Models, Animal; Genes, Dominant; Conserved Sequence; Animals; Amino Acid Sequence; Antigens, CD; Mutagenesis; Cerebellar Ataxia; Flow Cytometry