Table 3.

Bone phenotypes of Panx3 KO or knockdown mouse, zebrafish and avian models

Model	Age	Bone phenotypes
Global Panx3 KO Mouse Moon, Penuela [16, 43]	Neonatal	No growth plate abnormalities, deficits in bone mineral density or differences in the axial skeleton
	Young Adult	Shorter long bone diaphyses due to differences in allometric growth, but larger areas of muscle attachment and metaphyses/epiphyses in femora and humeri Femora and humeri are thicker and more robust, indicating they may have increased resistance to torsional and compressive forces
	Aged	Increased subchondral bone thickness in the medial compartment of knees and an altered subchondral collagen network with thicker collagen fibres Shortened appendicular skeleton
Panx3fl/fl:Col2cre Mouse (Cartilage-specific) [16]		No skeletal development or growth defects
Global Panx3 KO Mouse and panx3 knockdown zebrafish Oh [17]	Newborn	Bone abnormalities such as atypical curvatures, shortened long bone lengths, delayed ossification and lower levels of mineralization in early stages of bone development via intramembranous and endochondral ossification
	Young Adult	5–10% shorter bone lengths
Global Panx3 KO Mouse Ishikawa [26]	Newborn	Reduced bone density, shorter appendicular and axial bones and smaller skull bones with mineralization defects in the cranial vaults Ossification delays and altered mineralization were attributed to the role of PANX3 in the onset and normal progression of osteogenesis Delayed development of secondary ossification centres, indicating a reduction in vascular invasion Reduced osteocyte markers
Global Panx3 KO Mouse Yorgan [27]	Newborn	Reduced long bone length and severe, but nonlethal, skeletal deformities
	Adolescent and Adult	No differences in bone mineral density, trabecular bone mass, nor any structural skeletal abnormalities apart from a moderately reduced femur length, suggesting that despite delays in the onset of KO mouse mineralization, subsequent mineralization processes are unaffected No differences in osteoblast, osteocyte or osteoclast numbers
Panx3fl/fl:Runx2cre Mouse (Osteoblast-Specific) [27]	Adult	No trabecular abnormalities and normal bone formation rates Slightly decreased femoral cortical thickness
Avian Model [41]	Embryonic	No major skeletal phenotypic defects or differences in any bone differentiation markers to control animals with PANX3 overexpression or knockdown Reduced long bone volumes and slightly smaller ossification centres with PANX3 knockdown