Phenotypes Associated with This Genotype

Genotype
MGI:5604139

• Allelic Composition: Smad4^tm2.1Cxd/Smad4^tm2.1Cxd; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CD-1

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:211171 )

• almost none of the mutants survive to 8 weeks

• lethality is not alleviated by paste-formula food or by keeping pups with the mother

postnatal lethality, incomplete penetrance ( J:211171 )

• about 50% of pups die by P14 and almost none survive to 8 weeks

skeleton

abnormal osteoblast physiology ( J:211171 )

• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

abnormal tibia morphology ( J:211171 )

• tibia are small but morphologically normal

decreased diameter of tibia ( J:211171 )

• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls

short tibia ( J:211171 )

• at P28, tibias are about 22% shorter relative to controls

clavicle hypoplasia ( J:211171 )

abnormal long bone diaphysis morphology ( J:211171 )

• diaphyseal medullary space is inappropriately populated by an excessive amount of trabecular bone

rib fractures ( J:211171 )

• multiple rib fractures are seen at 8 weeks of age

abnormal bone collagen fibril morphology ( J:211171 )

• marker analysis indicates abnormal thickness or packing density of collagen fibers in tibia and delayed differentiation of osteoblasts

decreased bone mineral density ( J:211171 )

• craniofacial and axial skeleton are severely under mineralized

• bone mineral density in P28 tibias is reduced 20% relative to controls

• hypomineralized interparietal bones

abnormal compact bone lamellar structure ( J:211171 )

• cortical bone is primarily woven rather than lamellar

decreased compact bone thickness ( J:211171 )

• cortical thickness is decreased by 15%

abnormal osteocyte morphology ( J:211171 )

• osteocyte density is increased in the cortex of bones, but no differences in cancellous bone

abnormal trabecular bone morphology ( J:211171 )

• trabecular bone populates the entire diaphysis instead of being restricted to primary and secondary ossification centers

• trabecular structures in the diaphysis of tibiae are bone and not cartilage left behind during resorption of endochondral cartilage template

delayed bone ossification ( J:211171 )

craniofacial

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

growth/size/body

abnormal tooth morphology ( J:211171 )

• severe dental abnormalities

small incisors ( J:211171 )

• underdeveloped incisors at P28

abnormal enamel morphology ( J:211171 )

• yellow or even black dental discoloration typical of enamel hypoplasia

malocclusion ( J:211171 )

• mice develop oral malocclusion

small thoracic cavity ( J:211171 )

decreased body size ( J:211171 )

• pups are slightly smaller at birth and mice are severely runted by P28

hematopoietic system

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

immune system

decreased osteoclast cell number ( J:211171 )

• TRAP-positive osteoclasts are very sparse on the residual trabeculae, endocortical and periosteal surfaces of bones

limbs/digits/tail

abnormal tibia morphology ( J:211171 )

• tibia are small but morphologically normal

decreased diameter of tibia ( J:211171 )

• tibias are narrow at the mid-diaphysis with a total cross-sectional tissue area reduced 43% relative to controls

short tibia ( J:211171 )

• at P28, tibias are about 22% shorter relative to controls

cellular

abnormal osteoblast physiology ( J:211171 )

• osteoblasts do not function properly, depositing abnormal collagen into the skeletal extracellular matrix

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta		DOID:12347	OMIM:PS166200	J:211171