Ultrastructural analysis of development of myocardium in calreticulin-deficient mice.
BACKGROUND
Calreticulin is a Ca2+ binding chaperone of the endoplasmic reticulum which influences gene expression and cell adhesion. The levels of both vinculin and N-cadherin are induced by calreticulin expression, which play important roles in cell adhesiveness. Cardiac development is strictly dependent upon the ability of cells to adhere to their substratum and to communicate with their neighbours.


RESULTS
We show here that the levels of N-cadherin are downregulated in calreticulin-deficient mouse embryonic hearts, which may lead to the disarray and wavy appearance of myofibrils in these mice, which we detected at all investigated stages of cardiac development. Calreticulin wild type mice exhibited straight, thick and abundant myofibrils, which were in stark contrast to the thin, less numerous, disorganized myofibrils of the calreticulin-deficient hearts. Interestingly, these major differences were only detected in the developing ventricles while the atria of both calreticulin phenotypes were similar in appearance at all developmental stages. Glycogen also accumulated in the ventricles of calreticulin-deficient mice, indicating an abnormality in cardiomyocyte metabolism.


CONCLUSIONS
Calreticulin is temporarily expressed during heart development where it is required for proper myofibrillogenesis. We postulate that calreticulin be considered as a novel cardiac fetal gene.
Lozyk
Mira D
MD
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. mdlozyk@shaw.ca <mdlozyk@shaw.ca>
Papp
Sylvia
S
Zhang
Xiaochu
X
Nakamura
Kimitoshi
K
Michalak
Marek
M
Opas
Michal
M
D000818:Animals; D015820:Cadherins / Q000235:genetics; D037282:Calreticulin / Q000172:deficiency / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology / Q000254:growth & development*; D006325:Heart Atria / Q000254:growth & development / Q000648:ultrastructure; D006352:Heart Ventricles / Q000254:growth & development / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*
D015820:Cadherins; D037282:Calreticulin; C489083:Cdh2 protein, mouse