Submitted on August 17, 2006
Accepted on January 9, 2007
Cerebral angiogenic factors, angiogenesis, and physiological response to chronic hypoxia differ amongst four commonly used mouse strains
Nicole L Ward1*, Elizabeth Moore2, Kristen Noon2, Nicholas Spassil2, Erica Keenan3, Tammy L Ivanco4, and Joseph C LaManna2
1 Dermatology, Anatomy and Neurosciences, Case Western Reserve University, Cleveland, Ohio, United States
2 Anatomy, Case Western Reserve University, Cleveland, Ohio, United States
3 Pathology, Case Western Reserve University, Cleveland, Ohio, United States
4 Psychology, Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada
* To whom correspondence should be addressed. E-mail: nlw4{at}cwru.edu.
Angiogenesis is a critical element for adaptation to low levels of oxygen and occurs following long term exposure to mild hypoxia in rats. To test whether a similar response in mice occurs, CD1, 129/Sv, C57Bl/6, and Balb/c mice were exposed to 10% oxygen for up to 3 weeks. All mice showed significant increases in the percentage of packed red blood cells, and CD1 and 129/Sv mice showed increased respiration frequency and minute volume, common physiological measures of hypoxia. Significant angiogenesis was observed in all strains except Balb/c following 3 weeks exposure to chronic hypoxia. CD1 hypoxic mice had the largest increase (88%), followed by C57Bl/6 (48%), 129/Sv (41%), and Balb/c (12%) suggesting that some mice undergo more remodeling than others in response to hypoxia. Protein expression analysis of vascular endothelial growth factor (VEGF), angiopoietin (Ang)1 and 2, and Tie2 were examined in order to determine whether regulation of different angiogenic proteins could account for the differences observed in hypoxia-induced angiogenesis. CD1 mice showed the strongest upregulation of VEGF, Ang2, Ang1 and Tie2 whereas Balb/c had only subtle increases in VEGF and no change in the other proteins. C57Bl/6 mice showed a regulatory response that fell between the CD1 and Balb/c mice, consistent with the intermediate increase in angiogenesis. Our results suggest that genetic heterogeneity plays a role in angiogenesis and regulation of angiogenic proteins, and needs to be accounted for when designing and interpreting experiments using transgenic mice and when studying in vivo models of angiogenesis.
