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Characterization of Inducible SMC-specific Drosha Knockout Mice
Date
2015Type
ThesisDepartment
Biology
Degree Level
Honors Thesis
Degree Name
Biology
Abstract
Smooth muscle cells (SMCs) play an important role in the contraction of gastrointestinal
(GI) smooth muscles, generating spontaneous action potentials and forming electrical and
mechanical junctions coupling with interstitial cells. Recent studies have shown that
microRNAs (miRNAs), a new class of small RNAs that function as guide molecules in
RNA silencing, regulate and maintain the differentiation state of SMCs. A transgenic
animal model to study SMC-specific knockout of Dicer, one of two RNase III proteins in
miRNA biogenesis, showed that contractile motility in the mutant intestine was
dramatically decreased (Park, Yan, et al., 2011). The purpose of this study was to
investigate the function of Drosha, another of the two RNase III proteins in miRNA
biogenesis, in intestinal SMCs using a transgenic animal model. We generated SMCspecific
inducible Drosha null animals (smMHCCre-ERT2/+;Droshalox/lox) by cross-breeding
a smMHC/Cre/eGFP (smMHCCre-GFP/+) male mouse and a Droshalox/lox female
homozygote mouse. The inducible SMC-specific knockout (KO) mice caused severe
changes in phenotype and function of the GI tract. Morphological study of the GI smooth
muscle showed that the KO mice developed a thicker muscle layer of the intestinal tract
from the upper duodenum to the jejunum down to the whole colon. Histological serial
sections stained with hematoxylin and eosin (H&E) showed hypertrophy in both jejunum
and colon SM layers. This phenotype can be at least partially explained by the loss of
SMC-specific miRNAs, miR-143 and miR-145, identified as regulators of SMC growth
and/or differentiation. In conclusion, the data gathered in the present research suggests
that miRNAs are required for the proper maintenance of SMCs in the GI tract. Further
ii
research is needed to understand the complete molecular mechanisms required for
development and maintenance of contractile activity in SMCs in the GI tract.
Permanent link
http://hdl.handle.net/11714/546Additional Information
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