Expression and assembly of a human neurofilament protein in transgenic mice provide a novel neuronal marking system.
To investigate the regulation of neurofilament gene expression, we have generated several lines of transgenic mice carrying multiple copies of a cloned human neurofilament (NF-L) gene. We show that a 21.5-kb DNA fragment including the human NF-L gene contains essential information for correct expression in nervous tissue of transgenic mice. The integrated genes are arranged in multiple tandem arrays, but the extent of transgene expression does not correlate with copy number nor does it influence the expression of the endogenous neurofilament genes. However, the levels of human NF-L protein recovered in neurofilament preparations from brains of transgenic mice correlate directly with the relative abundance of human NF-L mRNA detected in each line. There is an apparent delay in the accumulation of human NF-L protein during development, as determined by immunoblotting with a human-specific monoclonal antibody. Finally, immunohistochemical localization of the human NF-L protein results in the specific staining of neurons and their processes in transgenic mice.
Julien
J P
JP
Institut du Cancer de Montréal, Centre Hospitalier Notre-Dame, Canada.
Tretjakoff
I
I
Beaudet
L
L
Peterson
A
A
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000254:growth & development; D004262:DNA Restriction Enzymes; D005786:Gene Expression Regulation; D007381:Intermediate Filament Proteins / Q000235:genetics*; D046911:Macromolecular Substances; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000254:growth & development; D016900:Neurofilament Proteins; D009474:Neurons / Q000502:physiology*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007381:Intermediate Filament Proteins; D046911:Macromolecular Substances; D016900:Neurofilament Proteins; D004262:DNA Restriction Enzymes