The motor neuron degeneration (mnd) gene acts intrinsically in motor neurons and peripheral fibroblasts.
In motor neuron degeneration (mnd/mnd) mice, multiple cell types develop cytopathology and motor neurons degenerate prematurely. Here, to investigate whether the expression of mnd within affected cells is responsible, we analyzed the evolution of cellular pathology in aggregation chimeras containing cells of both mnd/mnd and +/+ genotypes. In addition, skin fibroblasts were maintained in vitro in the absence of other cell types and examined for their disease manifestation. In the chimeras, neuronal genotype was identified by expression of an unrelated transgene. Consistent with an intrinsic action of mnd, the genotype and phenotype of motor neurons correlated perfectly. In addition, abnormal lipopigment accumulation, signifying the disease phenotype, evolved in the cultured fibroblasts. We conclude that neurons and fibroblasts develop pathological abnormalities in response to intrinsic expression of the mnd mutation. Further, as cellular pathology is not attenuated in the chimeric environment, it is unlikely that mnd and its human counterparts, neuronal caroid lipofuscinoses, will be responsive to a treatment strategy involving transplantation of normal cells.
Porter
J C
JC
Department of Pediatrics, Albany Medical College, New York 12208, USA.
Messer
A
A
Peterson
A
A
D000818:Animals; D002478:Cells, Cultured; D002678:Chimera / Q000276:immunology; D005347:Fibroblasts / Q000473:pathology*; D005796:Genes / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000473:pathology*; D009410:Nerve Degeneration / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology*