The development of respiratory control and hypoxic sensitivity in two inbred strains of mice
by Balbir, Alexander, Ph.D., THE JOHNS HOPKINS UNIVERSITY, 2008, 256 pages; 3309599

Abstract:

Firstly, we examined the ventilatory chemoreflex in 1-day, 1-week and 4-week old, male DBA/2J and A/J mice. We hypothesize that during development both strains demonstrate different sensitivity to hyperoxia and mild hypoxia during sleep with the DBA/2J strain having a more sensitive response. Our data demonstrate the A/J has a response to gases during development suggesting a functional CB. The magnitude of the response decreases with age in this strain. The DBA/2J strain demonstrates a gradual development in its response.

Secondly, we examined the specific sensitivity to chemical stimuli, using a superfused, ex-vivo approach that measures changes in CB, intracellular calcium ([Ca2+]i) levels using calcium fluorescence imaging techniques. We previously reported that the ventilatory response to hypoxia is established at 1W. We hypothesized: (1) with age, CB sensitivity to hypoxia increases and (2) the A/J's CB sensitivity to hypoxia during development will be less than that of the DBA/2J strain. Our data suggest that the specific CB sensitivity to hypoxia begins to develop at approximately 1W in both strains. However, sensitivity does not increase in the A/J strain.

Thirdly, we examined the structural and morphological development of the CB in the 1D, 1W and 4W DBA/2J and A/J mice. We hypothesize: (1) the DBA/2J's CB will grow in volume from 1D to 4W while the A/J's CB will not grow; and (2) the amount of GCs will increase with age in the DBA/2J strain but not in the A/J strain. The DBA/2J's CB has a normal pattern for growth and GC proliferation unlike the A/J strain. This may account for any changes in the hypoxic response during development.

Finally, microarray analysis was used to examine differences in gene expression between the DBA/2J's and A/J's CBs. We hypothesized: (1) genes related to CB function are expressed less in the A/J mice compared to DBA/2J mice; (2) gene expression levels of morphogenic and trophic factors of the CB are significantly lower in the A/J mice than DBA/2J mice. Through pathway analysis we have constructed a model which shows gene interactions and offers a roadmap to investigate CB development and hypoxic sensitivity.

 
AdviserMachiko Shirahata
SchoolTHE JOHNS HOPKINS UNIVERSITY
SourceDAI/B 69-04, p. , Sep 2008
Source TypeDissertation
SubjectsAnimal Physiology Biology
Publication Number3309599
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