TY - JOUR
T1 - Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice
T2 - Increased neurofilament density in axons Without affecting caliber
AU - Monteiro, Mervyn J.
AU - Hoffman, Paul N.
AU - Gearhart, John D.
AU - Cleveland, Don W.
PY - 1990/10
Y1 - 1990/10
N2 - We have generated transgenic mice containing additional copies of the murine NF-L gene in order to examine the consequences of neurofilament-L overexpression on axonal morphology. Founder mice were constructed to carry a transgene in which the presumptive 5′ promoter sequences of NF-L were replaced with the strong murine sarcoma virus long terminal repeat promoter. The transgenes were expressed prominently in several tissues, including skeletal muscle and kidney where NF-L accumulated to ∼2% of cell protein. This was not accompanied by an overt phenotype, except that expression in lens led to cataract formation. In the brains of these animals, transgene RNA levels exceeded the endogenous NF-L RNAs by up to 20-fold, although no additional protein accumulated, indicating posttranscriptional regulation of NF-L expression. However, in peripheral neurons transgene RNA was approximately fourfold higher than endogenous NF-L mRNAs, and a corresponding increase in NF-L subunits was found in axons arising from these neurons. Myelinated nerve fibers of transgenic animals contained increased numbers of NFs, assembled predominantly of NF-L. This was reflected in an increase in the density of axonal NFs; axonal caliber was not affected.
AB - We have generated transgenic mice containing additional copies of the murine NF-L gene in order to examine the consequences of neurofilament-L overexpression on axonal morphology. Founder mice were constructed to carry a transgene in which the presumptive 5′ promoter sequences of NF-L were replaced with the strong murine sarcoma virus long terminal repeat promoter. The transgenes were expressed prominently in several tissues, including skeletal muscle and kidney where NF-L accumulated to ∼2% of cell protein. This was not accompanied by an overt phenotype, except that expression in lens led to cataract formation. In the brains of these animals, transgene RNA levels exceeded the endogenous NF-L RNAs by up to 20-fold, although no additional protein accumulated, indicating posttranscriptional regulation of NF-L expression. However, in peripheral neurons transgene RNA was approximately fourfold higher than endogenous NF-L mRNAs, and a corresponding increase in NF-L subunits was found in axons arising from these neurons. Myelinated nerve fibers of transgenic animals contained increased numbers of NFs, assembled predominantly of NF-L. This was reflected in an increase in the density of axonal NFs; axonal caliber was not affected.
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U2 - 10.1083/jcb.111.4.1543
DO - 10.1083/jcb.111.4.1543
M3 - Article
C2 - 2120242
AN - SCOPUS:0025153538
SN - 0021-9525
VL - 111
SP - 1543
EP - 1557
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -