Biology Reference
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display a significant reduction in muscle mass and abnormal myofiber
morphology, ultimately leading to perinatal lethality. The reduction of
muscle mass is due to decreased skeletal muscle cell proliferation, rather
than an inability to pattern skeletal muscle or specific myofiber type.
3.1.2. Mouse cardiac muscle
The role of Dicer in heart development has been investigated by two studies
using Nkx2.5 Cre lines (
Saxena and Tabin, 2010
;
Zhao
et al
., 2007
), which
express Cre in the earliest identifiable cardiac progenitors present in the
cardiac crescent. Despite this early depletion of Dicer, the general pattern-
ing and formation of the heart are not severely affected. However, later
morphogenetic events are flawed, and resulting mice display a series of heart
phenotypes including underdevelopment of the ventricular myocardium,
pericardial edema, and defects in outflow tract alignment and chamber
septation. These findings are consistent with the results from a third study
that reported that later depletion of cardiac Dicer using MHC-Cre leads to
progressive dilated cardiomyopathy, heart failure, and postnatal lethality
(
Chen
et al
., 2008
).
3.1.3. Smooth muscle
Two groups have investigated the consequence of Dicer depletion in
smooth muscle during developing (
Albinsson
et al
., 2010
;
Pan
et al
., 2011
)
by using the SM22-cre line, which is expressed in arterial, venous, and
visceral smooth muscle cells. This loss of miRNA processing resulted in
dilated and thin-walled blood vessels caused by a reduction in cellular
proliferation and disarray of vascular architecture, leading to embryonic
lethality associated with extensive internal hemorrhage.
3.2. Muscle phenotypes of miRNA mutants
Since a sizable number of genetic mutations in muscle miRNAs have been
reported, I focus here on a description of their phenotypes and mention the
results of miRNA knockdown experiments where appropriate (see
Table 3.1
for a summary of muscle miRNA phenotypes). Consistent with
the
dicer
mutant phenotypes described above, elimination of individual
miRNAs leads to defects late in muscle development involving muscle
morphology and function rather than early events during muscle develop-
ment including mesoderm formation or muscle progenitor fate specifica-
tion. However, miRNAs may be playing redundant roles either with one
another or with protein-coding genes, as has been shown recently in
C. elegans
(
Alvarez-Saavedra and Horvitz, 2010
;
Brenner
et al
., 2010
).
Thus, conclusive evidence regarding the general role of miRNAs in muscle
development awaits the construction of compound miRNA mutants.
