Table II.

Phenotypes of Knockout (KO) and knockin (KI) mice

Mouse Model	Phenotypes	Other Information	Refs.
Ccn1 KO	Embryonic lethality Failure in chorioallantoic fusion in 30% of embryos Placental insufficiency; deficient vessel bifurcation at the chorioallantoic junction Hemorrhage; loss of large vessel integrity Severe atrioventricular septal defects	Aberrant apoptosis in vascular cells and cardiac cushion mesenchymal cells Haploinsufficiency leads to persistent ostium primum atrial septal defects in 20% of adults	33, 54
Ccn2 KO	Perinatal lethality Severe skeletal dysplasia, enlarged hypertrophic zones, impaired endochondral ossification decreased β-cells and increased glucagon+ cells in pancreas Pulmonary hypoplasia	Premature exit of chondrocytes from the cell cycle Delayed replacement with osteoblast Decreased expression of VEGF in the hypertrophic zones	56–58
Ccn3 KO	Viable and appear largely normal Modest, transient, and sexually dimorphic skeletal abnormalities	Enhanced neoinitimal thickening after photochemically induced thrombosis	24, 60
Ccn5 KO	Early embryonic lethality		61
Ccn6 KO	No phenotype in mice No Ccn6 mRNA detected in mice by Northern blotting or in situ hybridization	Mutations in human CCN6 cause the autosomal recessive disorder progressive pseudorheumatoid dysplasia	62, 160
Ccn1 KI (Ccn1dm/dm)	Viable, fertile, and developmentally normal Significantly resistant to TNFα or Fas-mediated hepatocyte apoptosis Lack senescent cells in skin wound healing, leading to exacerbated fibrosis	Express CCN1 unable to bind fibroblast receptors (α6β1-HSPG)	7, 8, 26
Ccn2 floxed	Deletion in early limb bud mesemchyme show transient osteopenia at 1 month Deletion in osteoblasts results in osteopenia in 6 month male mice		180
	Deletion in fibroblasts renders resistant to bleomycin-induced skin fibrosis		72
	Deletion in ovary and uterus results in impaired follicle development, steroidogenesis, and ovulation		59
Ccn2 high to low expression	9-fold overexpression causes embryonic death at E10–12 30% of normal expression are viable and normal		181