The role of DNase X in skeletal muscle addressed by targeted disruption of the gene in a mouse model

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" The role of DNase X in skeletal muscle addressed by targeted disruption of the gene in a mouse model "
Iran Rashedi

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	54014
Doc. No	:	TL23968
Call number	:	‭MR49058‬
Main Entry	:	Iran Rashedi
Title & Author	:	The role of DNase X in skeletal muscle addressed by targeted disruption of the gene in a mouse model\ Iran Rashedi
College	:	University of Manitoba (Canada)
Date	:	2008
Degree	:	M.Sc.
student score	:	2008
Page No	:	122
Abstract	:	DNase X is a DNase I-like endonuclease which is highly expressed in cardiac and skeletal muscles. The protein is highly similar to DNase I and exhibits the same enzymatic properties known for DNase I in vitro. A handful of previous studies has provided information on the cellular localization of the protein, and its biochemical and functional features as a DNA hydrolyzing enzyme; however, the biological role of DNase X is not yet known. To address the function of DNase X in vivo, we have generated a DNase X mutant mouse by targeted disruption of the gene. DNase X(-/-) mice are viable, fertile, and develop normally alter birth, though are lighter in body weight than their wild-type littermates. We have shown that DNase X is dispensable for skeletal muscle development, and macroscopic structure and morphology of muscles of the hindlimb in DNase X(-/-) mice are comparable with wild-type muscles. DNase X(-/-) mice displayed reduced fatigue tolerance when tested for their running performance. Histology revealed that a notable proportion of fibers in soleus of older DNase X (-/-) mice have evidence of damage/regeneration, which affected both slow and fast fibers equally. This phenotype was most noticeable in soleus but also appeared in some other leg muscles in DNase X(-/-) mice alter treadmill running whereas no similar changes were observed in any wild-type muscles studied. We carried out quantitative real time RT-PCR, and found no evidence of sex- and age-association in the expression of DNase X in skeletal muscle. We examined the possibility of functional redundancy by evaluating the mRNA expression profile of other members of DNase I family in DNase X(-/-) mice, and found no significant variation between the wild-type and mutant muscles. We also found that nuclease activity was diminished in tissue extracts of DNase X deficient muscles, whereas no similar difference was observed in other tissues. These findings suggest that DNase X is involved in the normal physiology of skeletal muscle by preventing age- and stress-related fiber damage in certain muscle types. This is the first report on DNase X mice; however, additional investigations will need to be performed to further characterize the muscle-specific phenotype in these mice, and to unravel the mechanisms contributing to this unique phenotype.
Subject	:	Biological sciences; Molecular biology; Genetics; Physiology; 0369:Genetics; 0433:Physiology; 0307:Molecular biology
Added Entry	:	University of Manitoba (Canada)