Animal models of osteogenesis imperfecta: applications in clinical research

Figures & data

Table 1 Current animal models for human osteogenesis imperfecta (OI), with their genetic and phenotypic characteristics and clinical therapy applications

Common name	Human OI type	Gene	Characteristics	Clinical therapy
Mouse models
Mov-13^−/−	OI II	COL1A1	Perinatal mortality	Gene replacement
Mov-13^/+	OI I	COL1A1	Hearing loss, reduced mechanical properties in bone, and reduced collagen production
oim/oim	OI III	COL1A2	Fragile bones, osteopenia, cortical thinning, bone deformities, joint laxity, kyphosis	Bisphosphonate therapy, stem cell transplantation, bone marrow stromal cells, gene supplementation, whole-body vibration
oim^/+	OI I	COL1A2	Decreased material properties of bone
G610C/G610C^Neo+	OI IV	COL1A2	Decreased body weight, bone mineral density, bone volume, and mechanical properties of bone
+/G610C^Neo+	OI I/IV	COL1A2	Decreased body weight, bone mineral density, bone volume, and mechanical properties of bone
+/G610C^Neo− (Amish)	OI IV	COL1A2	Decreased body weight, bone mineral density, bone volume, and mechanical properties of bone
G859C	OI II	COL1A1	Short and wavy ribs, poor bone mineralization, underdeveloped skeleton, pliable limbs, perinatal death
Aga2^/+	OI II/III	COL1A1	Skeletal deformities, fragile bones, osteopenia, perinatal death (in some cases)
Aga2^−/−	OI II	COL1A1	Embryonic mortality
BrtlII	OI II	COL1A1	Rib fractures, short vertebral bodies, poor skull mineralization, perinatal mortality
BrtlIV^/+	OI IV	COL1A1	Perinatal death to long-term survival, bone deformity, fragile bones, osteopenia	Bisphosphonate therapy, sclerostin antibody therapy, bone marrow stromal cells
BrtlIV/BrtlIV	OI IV (mild)	COL1A1	Bone deformity, bone fragility, osteopenia
Human COL1A1 minigene	OI II–IV	COL1A1	Fragile bones, low bone mineral density, ~90% perinatal mortality rate (when high levels of minigene expressed)	Bone marrow stromal cells, oligonucleotide antisense gene therapy
Ifitm5 transgenic	OI V	IFITM5	Skeletal deformities, fragile bones, poor bone mineralization, perinatal death
Pedf^−/−	OI VI	SERPINF1	Decreased material properties of bone
Crtap^−/−	OI VII	CRTAP	High bone mineralization and mineral density in bone (but low bone density), progressive kyphoscoliosis, cartilage dysplasia, decreased material properties in skin
P3h1^−/−	OI VIII	LEPRE1	Small body size, low mineral density in calvarial and long bones, decreased material properties of bone, impaired hearing
Ppib^−/−	OI IX	PPIB	Decreased body size and weight, low bone mineral density and volume, progressive kyphosis, decreased material properties in skin
Hsp47^−/−	OI X	SERPINH1	Embryonic mortality
Fkbp10^−/−	OI XI	FKBP10	Delayed growth beginning at E13.5, fragile tissue, skeletal deformities, perinatal mortality
Sp7^−/−	Possibly OI XII	SP7	Decreased trabecular bone mineralization, osteopenia, cortical bone thinning
Wnt1^Sw/Sw (Swaying)	OI XV	WNT1	Poor coordination, osteopenia, fragile bones, cerebellar deficit
Canine models
G208A Col1a1 Golden Retriever	OI III	COL1A1	Fragile bones, dentinogenesis imperfecta
Col1a2 frameshift Beagle	OI III	COL1A2	Fragile bones
SerpinH1 (L326P) Dachshund	OI X	SERPINH1	Fragile bones, lameness, thin cortical bone and dentine
Zebrafish models
Med^−/−	OI I–IV	COL1A1	Delayed bone ossification and low bone mineral density, larval fin undulation, curtain-like waves in fin epithelium
Chi^/+	OI I–IV	COL1A1	Generalized defective bone growth
Chi/Chi	OI I–IV	COL1A1	Generalized defective bone growth
Frf^−/−	OI XIII	BMP1	Ruffled larval fin, short body axis, deformed craniofacial bones and vertebrae, reduced ossification and bone density