| First Author | Rashedi I | Year | 2008 |
| Journal | Master's Thesis - University of Manitoba | Mgi Jnum | J:243709 |
| Mgi Id | MGI:5910222 | Citation | Rashedi I (2008) The role of DNase X in skeletal muscle addressed by targeted disruption of the gene in a mouse model. Master's Thesis - University of Manitoba |
| abstractText | DNase X is a DNase l-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 vÃtro. 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(rl mice are viable, fertile, and develop normally after 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 after 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 null mice; however, additional investigations will need to be performed to further charactenze the musclespecific phenotype in these mice, and to unravel the mechanisms conhibuting to this unique phenotype. |
