Phenotypes Associated with This Genotype

Genotype
MGI:4818953

• Allelic Composition: Suco^{Gt(KST050)Byg}/Suco^{Gt(KST050)Byg}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

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

Suco^{Gt(KST050)Byg}/Suco^{Gt(KST050)Byg} mice exhibit growth retardation and low bone mass with multiple fractures

mortality/aging

postnatal lethality, complete penetrance ( J:159823 )

• over 80% mortality by P10 with no mice surviving to weaning

neonatal lethality, incomplete penetrance ( J:159823 )

• Background Sensitivity: about 50% die neonatally on a mixed 129P2/OlaHsd, C57BL/6, and CD-1 background compared to 100% lethality on a mixed 129P2/OlaHsd and C57BL/6 background

respiratory system

respiratory distress ( J:159823 )

skeleton

abnormal cranium morphology ( J:159823 )

abnormal neurocranium morphology ( J:159823 )

• flatter compared to controls

thin neurocranium ( J:159823 )

• markedly thinner at P10

decreased osteoclast cell number ( J:159823 )

• in femurs

abnormal long bone morphology ( J:159823 )

• at P5 long bones are misshapen

abnormal bone collagen fibril morphology ( J:159823 )

• at P10 cortical bone resembles immature woven bone with sparse and randomly oriented type I collagen fibrils

abnormal compact bone morphology ( J:159823 )

• modest decrease in the amount of cortical bone in neonates

decreased compact bone thickness ( J:159823 )

• dramatically thinner cortices in long bones at P10

abnormal osteoblast morphology ( J:159823 )

• small immature osteoblasts are present in fracture calluses

• at P10 in tibiae osteoblasts lack extensive, well-organized rough endoplasmic reticulum (rER) cisternae

• osteoblasts have a fibroblastic appearance with a scarce, discontinuous rER network and a higher nuclear/cytoplasmic ratio

increased osteocyte number ( J:159823 )

• expression analysis indicates an increase in osteocyte numbers

abnormal trabecular bone morphology ( J:159823 )

• decrease in the amount of trabecular bone in neonates and at P10

• decrease in the number of trabeculae and increase in trabecular separation at P10

decreased bone trabecula number ( J:159823 )

decreased trabecular bone connectivity density ( J:159823 )

decreased trabecular bone thickness ( J:159823 )

• at P10

decreased bone mass ( J:159823 )

abnormal joint morphology ( J:159823 )

• inflexible joints at P5

wide cranial sutures ( J:159823 )

• wider sutures in the cranial vault

abnormal skeleton development ( J:159823 )

• modestly delayed in neonates

impaired osteoblast differentiation ( J:159823 )

• in vivo and in culture osteoblasts display impaired differentiation

abnormal skeleton physiology ( J:159823 )

abnormal bone healing ( J:159823 )

• hyperplastic calluses consist largely of calcified cartilage with small, immature osteoblasts present throughout the callus and fracture site but mature osteoblasts and newly formed bone are absent

abnormal bone ossification ( J:159823 )

• labeling with calcein, a marker of newly formed bone, results in punctate discontinuous labeling rather than the regular labeling seen in wild-type controls

• however, bone that does form is properly mineralized

delayed bone ossification ( J:159823 )

• in neonates

delayed endochondral bone ossification ( J:159823 )

• in neonates

delayed intramembranous bone ossification ( J:159823 )

• in neonates

abnormal bone remodeling ( J:159823 )

abnormal osteoblast physiology ( J:159823 )

• primary calvarial osteoblasts show reduced alkaline phosphatase activity, sparsely formed collagen matrix, and significantly fewer bone nodules

• in culture primary calvarial osteoblasts grow faster but display impaired differentiation potential compared to wild-type osteoblasts

• decrease in the synthesis of type I collagen chains

increased osteoblast apoptosis ( J:159823 )

• modest increase in osteoblast apoptosis

abnormal osteoclast physiology ( J:159823 )

• expression analysis indicates decreased osteoclast activity

fragile skeleton ( J:159823 )

• spontaneous fractures are seen at P5

• hyperplastic calluses suggesting ongoing fracture repair are seen throughout the axial and appendicular skeleton

growth/size/body

decreased body size ( J:159823 )

postnatal growth retardation ( J:159823 )

• failure to thrive

decreased fetal size ( J:159823 )

• at E18.5

behavior/neurological

impaired righting response ( J:159823 )

abnormal gait ( J:159823 )

• imbalanced gait

cardiovascular system

internal hemorrhage ( J:159823 )

• around the forelimbs and cervical vertebrae at P5

spinal hemorrhage ( J:159823 )

• around the cervical vertebrae at P5

homeostasis/metabolism

hypoglycemia ( J:159823 )

• hypoglycemia without hyperinsulinemia

decreased circulating insulin-like growth factor I level ( J:159823 )

decreased circulating osteocalcin level ( J:159823 )

• decrease in the serum level of osteocalcin, the definitive marker of mature osteoblasts at P5 and P10

increased circulating alkaline phosphatase level ( J:159823 )

abnormal bone healing ( J:159823 )

• hyperplastic calluses consist largely of calcified cartilage with small, immature osteoblasts present throughout the callus and fracture site but mature osteoblasts and newly formed bone are absent

renal/urinary system

abnormal renal glomerulus morphology ( J:159823 )

• modest glomerular hypercellularity

immune system

decreased osteoclast cell number ( J:159823 )

• in femurs

abnormal osteoclast physiology ( J:159823 )

• expression analysis indicates decreased osteoclast activity

hematopoietic system

decreased osteoclast cell number ( J:159823 )

• in femurs

abnormal osteoclast physiology ( J:159823 )

• expression analysis indicates decreased osteoclast activity

craniofacial

abnormal cranium morphology ( J:159823 )

wide cranial sutures ( J:159823 )

• wider sutures in the cranial vault

abnormal neurocranium morphology ( J:159823 )

• flatter compared to controls

thin neurocranium ( J:159823 )

• markedly thinner at P10

nervous system

spinal hemorrhage ( J:159823 )

• around the cervical vertebrae at P5

cellular

impaired osteoblast differentiation ( J:159823 )

• in vivo and in culture osteoblasts display impaired differentiation

abnormal osteoblast physiology ( J:159823 )

• primary calvarial osteoblasts show reduced alkaline phosphatase activity, sparsely formed collagen matrix, and significantly fewer bone nodules

• in culture primary calvarial osteoblasts grow faster but display impaired differentiation potential compared to wild-type osteoblasts

• decrease in the synthesis of type I collagen chains

increased osteoblast apoptosis ( J:159823 )

• modest increase in osteoblast apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteogenesis imperfecta type 5		DOID:0110344	OMIM:610967	J:159823