Rat tau proteome consists of six tau isoforms: Implication for animal models of human tauopathies

Axon Neuroscience GmbH, Rennweg, Vienna, Austria.
Journal of Neurochemistry (Impact Factor: 4.28). 02/2009; 108(5):1167-76. DOI: 10.1111/j.1471-4159.2009.05869.x
Source: PubMed


Human brain encompasses six tau isoforms, containing either three (3R) or four (4R) repeat domains, all of which participate in the pathogenesis of human tauopathies. To investigate the role of tau protein in the disease, transgenic rat models have been created. However, unlike humans, it has been suggested that rat brain expresses only three 4R tau isoforms. Because of the significance of the number of tau isoforms for faithful reproducibility of neurofibrillary pathology in transgenic rat models, we reopened this issue. Surprisingly, our results showed that adult rat brain contains six tau isoforms like humans. Protein expression of 4R tau isoforms was ninefold higher than 3R isoforms. Furthermore, the protein levels of tau isoforms with none, one or two N-terminal inserts were 30%, 35%, and 35% of total tau, respectively. Moreover, amount and ratio of tau isoforms were developmentally regulated. The levels of 4R tau isoforms progressively increased from early postnatal period until adulthood, whereas the expression of 3R tau isoforms reached maximum at P10 and then gradually declined. Our results show that rat brain encompasses full tau proteome similar to humans. These findings support the use of rat as an animal model in human tauopathies research.

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Available from: Jozef Hanes, Oct 16, 2014
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    • "First, rats are genetically, phys- 62 iologically and morphologically closer to humans than 63 mice (Gibbs et al., 2004). Second, rats express the six 64 isoforms of tau protein-like expressed in humans and 65 the rat apoE amino acid sequences show a higher level 66 of homology to its human counterpart (McLean et al., 67 1983; Hanes et al., 2009). Finally, behavior tests are 68 much better characterized for rats, allowing a more accu- 69 rate assessment of the memory and cognition impair- 70 ments associated with AD (Lecanu and Papadopoulos, 71 2013). "
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