Deficiency of annexins A5 and A6 induces complex changes in the transcriptome of growth plate cartilage but does not inhibit the induction of mineralization.
Initiation of mineralization during endochondral ossification is a multistep process and has been assumed to correlate with specific interactions of annexins A5 and A6 and collagens. However, skeletal development appears to be normal in mice deficient for either A5 or A6, and the highly conserved structures led to the assumption that A5 and A6 may fulfill redundant functions. We have now generated mice deficient of both proteins. These mice were viable and fertile and showed no obvious abnormalities. Assessment of skeletal elements using histologic, ultrastructural, and peripheral quantitative computed tomographic methods revealed that mineralization and development of the skeleton were not significantly affected in mutant mice. Otherwise, global gene expression analysis showed subtle changes at the transcriptome level of genes involved in cell growth and intermediate metabolism. These results indicate that annexins A5 and A6 may not represent the essential annexins that promote mineralization in vivo.
Belluoccio
Daniele
D
Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, and Royal Children's Hospital, Parkville, Victoria, Australia.
Grskovic
Ivan
I
Niehoff
Anja
A
Schlötzer-Schrehardt
Ursula
U
Rosenbaum
Sabrina
S
Etich
Julia
J
Frie
Christian
C
Pausch
Friedericke
F
Moss
Stephen E
SE
Pöschl
Ernst
E
Bateman
John F
JF
Brachvogel
Bent
B
D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017317:Annexin A6 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000918:Antibody Specificity; D001846:Bone Development / Q000235:genetics; D001857:Bone Matrix / Q000378:metabolism / Q000648:ultrastructure; D002113:Calcification, Physiologic / Q000235:genetics*; D002356:Cartilage / Q000378:metabolism* / Q000648:ultrastructure; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D005269:Femur / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D017304:Annexin A5; D017317:Annexin A6; D003094:Collagen