Age-related changes in tau protein isoform expression in mice brains.

摘要

Tau is a microtubule-associated protein important for the assembly and stabilization of microtubules. Six tau isoforms are produced in the central nervous system from one single gene as a result of the alternative splicing of exons 2, 3 (N-terminal part) and exon 10 (C-terminal part). The shortest isoform (2-3-10-, 0N 3R) is characteristic for fetal brains, whereas the remaining (2+3-10-, 1N 3R; 2+3+10-, 2N 3R; 2-3-10+, 0N 4R; 2+3-10+, 1N 4R; 2+3+10+, 2N 4R) for adult brains. The aim of the study was to establish a profile of tau protein variants in the C57BL/6J mouse frontal cortex during the aging process. The total RNA was isolated from tissues, followed by reverse transcription and PCR reaction. It was found that the sequence encoded by exon 10 was absent in the youngest mice (5-day-old newborns, isoform 3R), while it was present in 21-, 70- and 140-day-old animals (isoform 4R). The most abundant isoform in 5-day-old mice was IN and accounted for 66% of the total tau protein. The percentage of IN isoforms lowered with age and was 31% in 140-day-old animals. The total percentage of ON isoforms was 11% in 5-day-old mice and was approximately three-fold lower than in each of the older groups. It is concluded that alternative splicing of the tau protein undergoes age-dependent regulation in the mouse brain cortex..