The hypothesis that myelin-associated glycoprotein (MAG) initiates myelin formation is based in part on observations that MAG has an adhesive role in interactions between oligodendrocytes and neurons. Furthermore, the over- or underexpression of MAG in transfected Schwann cells in vitro leads to accelerated myelination or hypomyelination, respectively. Here we test this idea by creating a null mutation in the mag locus and deriving mice that are totally deficient in MAG expression at the RNA and protein level. In adult mutant animals the degree of myelination and its compaction are normal, whereas the organization of the periaxonal region is partially impaired. Mutant animals show a subtle intention tremor. Our findings do not support the widely held view that MAG is critical for myelin formation but rather indicate that MAG is necessary for maintenance of the cytoplasmic collar and periaxonal space of myelinated fibres.
The site of integration of transgenes in the host genome can affect levels of expression and occasionally confer ectopic patterns of expression on otherwise tissue-specific genes. We describe here a line of mice in which an hsp68-lacZ transgene is expressed in unstressed developing neural tissue and where the transgene insertion has caused a mutation of a neural tissue-specific gene, dystonia musculorum (dt). This coincidence suggests that expression of the hsp68-lacZ construct may be controlled directly by cis-acting regulatory sequences that normally control the developmental expression of the dt gene. Such constructs may serve as useful tools for identifying new tissue-specific enhancers and their associated genes.
Lineage-specific regulatory elements can be used to direct expression of a variety of genes to specific tissues in transgenic mice. If the hybrid constructs contain a gene encoding a cytotoxic gene product, then genetic ablation of a specific cell lineage can be achieved. We have generated six transgenic mice by introducing into fertilized eggs the mouse gamma 2-crystallin promoter fused to the coding region of the diphtheria toxin A-chain gene. Three of these mice and all the transgenic offspring analyzed were microphthalmic. The lenses of these mice displayed considerable heterogeneity: some were almost normal morphologically but reduced in size, whereas others were grossly aberrant and deficient in nuclear fiber cells. These studies indicate that programmed ablation of specific cell types can be stably transmitted through the germ line.
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