Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. We have identified and cloned a gene encoded at the dt locus. The product of the dt gene, dystonin, is a neural isoform of a hemidesmosomal protein bullous pemphigoid antigen 1 (bpag1). To investigate the potential role of dystonin in human neuropathies, we have cloned the neural-specific 5' exons of the human DT gene that together with the previously cloned BPAG1 sequences comprise human dystonin. The mouse and human dystonin genes demonstrate the same spectrum of alternatively spliced products, and the amino acid sequences of the neural-specific exons in the mouse and human genes are over 96% identical.
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PMID:Cloning and characterization of the neural isoforms of human dystonin. 857 75

Ablation of the BPAG1 gene results in the dystonia musculorum mouse, exhibiting rapid spinal nerve degeneration, dystonic movements, and severe ataxia. By defining the developmental and tissue-specific expression of the neuronal form of BPAG1 (BPAG1-n) and by comparing the corresponding pathology in BPAG1 null mice, we seek here to understand how absence of BPAG1 results in this devastating phenotype in mice and in potentially related human neurological disorders. Throughout normal development, BPAG1-n was expressed in a variety of sensory and autonomic neuronal structures, but was absent or reduced in areas such as basal ganglia that are often affected in dystonias and ataxias. Interestingly, BPAG1-n was also expressed broadly in embryonic motor neurons, but expression declined dramatically after birth. Despite these complex developmental patterns, BPAG1-/- pathology was restricted largely to postnatal development. Moreover, gross neuronal degeneration was restricted to only a few regions where BPAG1-n was found, including dorsal root ganglion neurons and a small subset of motor neurons. Most notably, while skeletal muscle was normal, appearance of severe dystonic ataxia correlated with postnatal degeneration of muscle spindles. Collectively, our findings suggest a mechanism for the BPAG1 null phenotype and indicate that different neurons respond differently to the absence of BPAG1-n, a cytoskeletal linker protein.
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PMID:Developmental expression of BPAG1-n: insights into the spastic ataxia and gross neurologic degeneration in dystonia musculorum mice. 924 12