Alternative splicing of amino-terminal Tau mRNA in rat spinal cord during development and following axonal injury.
Tau is a family of microtubule-associated phosphoproteins in which isoform variation is produced by alternative splicing of a single gene and posttranslational modifications. Tau isoforms that include exon 10 are overexpressed in frontotemporal dementia and progressive supranuclear palsy. Therefore, we examined the expression of tau mRNA splice variants during axonal regeneration and abortive regeneration. Previous work in our laboratory demonstrated that expression of exon 10 tau isoforms during regeneration and abortive regeneration was altered and partially recapitulated the developmental patterns of tau isoform expression. Using RT-PCR, we examined the alternative splicing of exons 2 and 3 in tau during early postnatal development and regeneration in the rat spinal cord. The levels of tau lacking exons 2 and 3 were high on the day of birth and rapidly declined. Conversely, tau isoforms containing exon 2 or exons 2 and 3 first appeared at low levels and steadily increased. During axonal regeneration, the levels of all three tau mRNA isoforms were significantly lower 7 days after injury. In a model of abortive regeneration, all of the tau isoforms were elevated 14 and 42 days postinjury. The relative levels of exon 2 and 3 tau splice variants were not altered during regeneration or abortive regeneration as occurred during development. These results suggest that tau isoform expression following neuronal injury does not recapitulate the developmental pattern and is not independently regulated as in development. Our previous results together with these data suggest that alterations in tau mRNA isoform expression that occur in neurodegeneration are not secondary to axonal injury but may be a more primary event underlying cytoskeletal derangement.
Halverson
R A
RA
Department of Pharmacology, Loyola University Medical Center, 2160 South First Avenue, Maywood, Illinois, 60153, USA.
Chambers
C B
CB
Muma
N A
NA
D000375:Aging / Q000378:metabolism*; D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism; D019771:Axotomy; D005260:Female; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020426:Sciatic Neuropathy / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D012333:RNA, Messenger; D016875:tau Proteins