2006 Fiscal Year Final Research Report Summary
Study of congenital central respiratory failure using mice model
| Project/Area Number |
16500280
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Showa University |
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Principal Investigator |
ARATA Satoru Showa University, Center for Biotechnology, lecture, 組換えDNA実験室, 講師 (20159502)
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| Co-Investigator(Kenkyū-buntansha) |
ONIMARU Hiroshi Showa University, School of Medicine, Dpt. of Physiology, Associate professor, 医学部, 助教授 (30177258)
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| Project Period (FY) |
2004 – 2006
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| Keywords | respiratory failure / brainstem-preparation / gene deficient mice |
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| Research Abstract |
In order to search the genes which cause a human congenital respiratory failure, we have been studying by the following methods using wild mice and several lines of gene deficient mice that exhibit respiratory failure. 1)For the assessment of respiratory abnormality, ventilatory parameters were checked out by whole body plethysmography using prenatal and neonatal mice. 2)To clarify the mechanism of the respiratory failure, the respiratory neuron activity was examined by electrophysiological analysis and optical imaging analysis using the brainstem-spinal cord preparation. 3)To search for the genes that relate the central respiratory failure in brainstem, the alteration of gene expression in the medulla oblongata during transition from embryonic respiration to external respiration was examined by DNA microarray. Until now, we have studied several lines of gene deficient mice exhibit respiratory failure and proposed the several models of central respiratory failure and peripheral respiratory failure. For example, we previously reported that Tlx3 deficient mice die within 24hrs after birth from a central hypoventilation. Here, we demonstrated that the excess GABA-mediated inhibition caused dysfunction of respiratory neuronal network on Tlx3-/- mice. Also homeobox gene Pbx3 deficient mice die within 24hrs after birth from a central hypoventilation. Pbx3 seems to be correlated with Tlx3, however, Pbx3-/- mice showed a different respiratory disorder. Furthermore, we demonstrated that DSCAM (Down syndrome cell adhesion molecule) -/- mice die from a central hypoventilation with another respiratory pattern. As observed above, our approach seems to be useful in analysis of respiratory familiar.
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