Biology Reference
In-Depth Information
b
mice. Most studies to date regarding the function of
arrs during embryo-
genesis have been performed in lower model organisms.
2.
b
-ARRESTINS IN MODEL ORGANISMS
Most studies aiming to understand the function of
arrs during
embryogenesis have been undertaken in
Xenopus
, zebrafish, and flies. All
these models feature at least one
b
arr
gene (
Fig. 9.1
). While
Drosophila
exhibits a single
b
arr
gene, which is named
kurtz
,
13
two
b
arrs
have been
reported in
Xenopus.
14,15
The zebrafish genome harbors three
b
arrs, namely
b
arr1
,
b
arr2a
, and
b
arr2b
due to
b
arr2
gene duplication. So far, however,
only two of the three zebrafish
b
b
arrs have been analyzed, and it is not clear
if the two
b
arr2
genes differ functionally. Despite the duplication,
arrs in
lower vertebrates are closely related to their mammalian homologs, as can
be seen by phylogenetic comparison (
Fig. 9.1
). In addition, the genomic
arrangement of the
b
arr
locus is rather conserved between species. Thus,
aquatic models, such as frogs and zebrafish, can be considered valid models
for the analysis of
b
arr function in embryonic development.
This comes in handy, particularly as the ease of manipulation and rapid
generation of loss-of-function animals make
Xenopus
and zebrafish very
attractive model organisms for developmental studies. The embryos of both
frogs and zebrafish develop extrauterine, with accelerated development dur-
ing early embryogenesis. Both species produce embryos in great numbers,
which by simple injection of nucleic acids can be used for knockdown as
well as overexpression studies. Functional loss- or gain-of-function studies
can thus be realized in a time frame similar to cell culture studies but with the
advantage of an
in vivo
context. Interestingly, loss of single
b
arrs in aquatic
models does result in developmental phenotypes (see below; Refs.
14-19
).
This sets
Xenopus
and zebrafish apart frommice, where deletion of both
b
arrs
is required to interfere with organogenesis.
9,10
One explanation for this dis-
crepancy might be that all studies in zebrafish and
Xenopus
so far have been
done using transient knockdown approaches rather than complete loss-
of-function technologies. Knockdowns do not result in 100% depletion
of protein. Hence, residual protein in knockdown animals may be sufficient
to prevent the activation of compensating mechanisms by another
b
arr iso-
form. In KO mice, on the other hand, the targeted gene is not expressed at
all and the developing embryo will try to activate molecular bypasses such as
compensation by other genes of the same protein family. Furthermore, both
Xenopus
and zebrafish carry maternal protein from their yolk. In most cases,
b
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