The twitcher mouse: a model for Krabbe disease and for experimental therapies.

The twitcher is a naturally-occurring mouse mutant caused by an abnormality in the gene coded for galactosylceramidase. It is therefore genetically equivalent to human globoid cell leukodystrophy (Krabbe disease). Affected mice develop clinical symptoms at the onset of the active myelination period and, if untreated, die by 35 +/- days. The pathology is very similar to that in human disease. Toxicity of galactosylsphingosine (psychosine) that accumulates abnormally in the nervous system is considered to be primarily responsible for the pathogenesis. Transplantation of bone marrow cells from normal donors is partially effective and triples the life span of affected mice to 100 +/- days with evidence of remyelination in the CNS. The mutation responsible for the twitcher mutant has recently been identified. It is expected that this model will be useful for basic studies on treatment of this group of genetic disorders affecting the brain through transgenic and/or gene therapy approaches.