Altered microtubule-associated tau messenger RNA isoform expression in livers of griseofulvin- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated mice
L. Kenner et al., Altered microtubule-associated tau messenger RNA isoform expression in livers of griseofulvin- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated mice, HEPATOLOGY, 29(3), 1999, pp. 793-800
Tau proteins belong to the family of microtubule-associated proteins (MAPs)
, which so far have been mostly detected in neuronal cells. Different domai
ns on the protein serve different functions. By alternative splicing, sever
al mRNAs and tau isoforms are created from one gene, which contain these fu
nctionally important domains to various degrees, and thus differ in their m
icrotubule-related properties. In the present article, several novel observ
ations are reported. Tau mRNA and proteins have been identified and further
characterized in mouse liver. It is shown on the basis of mRNA determinati
ons that at least three tau isoforms differing particularly with respect to
their aminoterminal domains are present in mouse liver. The major and pred
ominant isoform (isoform 1) lacks portions encoded by exons 2 and 3, which
are responsible for cross-talk of microtubules with their environment ("pro
jection domain"). Moreover, mRNA encoding tau protein with four repeats of
the microtubule binding domain predominate in embryonal as well as adult mo
use liver in contrast to brain, in which a shift from the predominant three
-repeat isoform to the four-repeat isoform characterizes the transition fro
m the embryonic to the adult stage. Intoxication with griseofulvin (GF) or
3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) significantly affects in a
reversible manner the levels of tau mRNA as well as isoform ratios in mouse
liver, but not in mouse brain. Tau mRNAs are significantly increased in in
toxicated mouse livers. Moreover, a shift to isoform I lacking exons 2 and
3 occurs. However, the increase in liver tau protein was less than expected
from increased mRNA levels, which could be the result of translational or
posttranslational regulation. The consequences on microtubular function are
as yet unclear, but impairment can be expected because the overexpressed t
au mRNA isoform lacks the domain that mediates interaction of microtubules
with their environment. On the other hand, the ratio of polymerized (microt
ubules) to nonpolymerized tubulin remained unaffected.