Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 185

( Cheever et al., 2012 ). The reason or reasons for the perinatal lethality are
not clear, although even subtle behavioral or other differences between
β-actin KO and control pups could result in the KO pups being ignored or
even cannibalized. Those CNS- Actb KO pups that did survive were about
two-thirds the size of control littermates despite the fact that they had a
significantly higher caloric intake. Interestingly, this is very similar to what
was observed in the inducible Ate1 KO mice ( Brower andVarshavsky, 2009 ),
raising the possibility that the loss of arginylated β-actin is a factor in this
phenotype. Both mouse models exhibited profound hyperactivity and
despite an increased caloric intake, still exhibited stunted growth. Impaired
hypothalamic function and regulation of hunger could also be a factor
in both of these mouse models, although hypothalamic function was not
directly investigated in CNS- Actb KO mice. Yet, in contrast to the Ate1 KO
mouse model, CNS- Actb KO brains were proportionally smaller than con-
trol littermates, thus confirming that Ate1 has significant functions beyond
just the arginylation of β-actin.
6.1.2. Restricted Roles for β -Actin in Mediating Brain Structure
As stated in the introduction to this section, with the widely held hypoth-
esis that β-actin specifically regulates directional cell migration, it could be
predicted that histological examination of the brains from CNS- Actb KO
mice would reveal profound disorganization given the large amount of cell
migration required to properly assemble the brain. Thus, we were quite
surprised to find that the vast majority of the brain in CNS- Actb KO mice
was histologically indistinguishable from controls ( Cheever et al., 2012 ).
Proper cell layering in CNS- Actb KO brains could be seen in the normal
organization of the molecular and granule cell layer in the cerebellum, in
the pyramidal neuron layers in the hippocampus, as well as in the six cortical
layers of the cortex. Collectively, these data suggest that most if not all neu-
ronal migration does not require β-actin. However, because the migration
of some neurons is completed relatively early in development ( Ayala et al.,
2007 ), it cannot be ruled out that the low levels of β-actin still present soon
after Cre-mediated recombination were sufficient to drive normal neuronal
migration. Given that the Nestin-Cre line used is one of the earliest lines
available for neuronal specific expression, technological advances will likely
be required to definitively rule out a role for β-actin in early neuronal
migration.
In our analyses of the cerebellum and hippocampus, however, we did
observe striking yet highly localized morphological abnormalities. In the