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The Ig superfamily member NrCAM is believed to help orchestrate neuronal development, so Moré et al. (page 187) were surprised at the phenotype of their recently generated NrCAM -/- mice; the animals appear to have nearly normal nervous systems, but develop cataracts.' L& Q# [9 R+ o$ h& E
" y& {/ \ D. ?3 |9 h9 hThe mice are slightly smaller than their heterozygous littermates and show a slight motor defect, but are viable and fertile, and lack any histological abnormalities in any neural tissues. Their commissural axons cross the spinal cord midline normally, an unexpected result because previous work had suggested a requirement for NrCAM in directing commissural axon growth.
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, O; x2 a W- JWhile the absence of NrCAM does not appear to cause serious problems in neuronal tissue, NrCAM -/- mice develop cataracts because of a failure in establishing contact between lens fiber cells, and thus presumably a failure in forming normal water channels. Flow through these channels appears to be important for lens clarity, and defects in communication between lens fiber cells in the eye leads to the breakdown of the cells. Mice lacking ankyrin-B display a similar disorganization in the lens fiber, providing genetic evidence that NrCAM function requires a link to the cytoskeleton via ankyrin. The new work is also the first demonstration of NrCAM expression in the lens.' o, ?0 |/ {) b5 N
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Cataracts are the most common cause of visual impairment in humans. If mutations in human NrCAM or ankyrin-B are also involved in the formation of cataracts, then drugs or gene therapy strategies targeting these proteins might be medically important.(Cataracts form in mice lacking NrCAM.) |
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发表于 2009-3-5 23:31
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