Phenotypes Associated with This Genotype

Genotype
MGI:6195291

• Allelic Composition: Ifitm5^em1Pmof/Ifitm5⁺
• Genetic Background: involves: CD-1

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

mortality/aging

neonatal lethality, complete penetrance ( J:255349 )

• mice die at birth

skeleton

impaired osteoblast differentiation ( J:255349 )

• severe blunting of osteoblastogenesis, characterized by the persistence of a full unresorbed and mineralized cartilage enlagen throughout the midshaft of long bones

• the bone collar and primary ossification center do not form, suggesting early blunted osteoblast differentiation

abnormal osteoblast physiology ( J:255349 )

• cultured osteoblasts mineralize less than wild-type osteoblasts on day 7 and 14 of culture but are similar to wild-type by day 20

abnormal neurocranium morphology ( J:255349 )

• calvaria shows a reduction in the mineralization of parietal, frontal, and nasal regions

mandible hypoplasia ( J:255349 )

• mandible is hypoplastic and hypomineralized

• however, the mandible Meckel cartilage appears normal

short mandible ( J:255349 )

• mandible is 25-50% shorter

abnormal osteoclast morphology ( J:255349 )

• osteoclasts are only present in the restricted wedge-like structure at the midshaft region compared to wild-type where they are abundant throughout the marrow space

bowed radius ( J:255349 )

bowed ulna ( J:255349 )

bowed tibia ( J:255349 )

clavicle hypoplasia ( J:255349 )

• clavicle is hypoplastic and hypomineralized, being 25-50% shorter

abnormal long bone diaphysis morphology ( J:255349 )

• E17.5 humeri shaft shows almost complete absence of a marrow cavity and a wedge-like structure at the midshaft

increased width of hypertrophic chondrocyte zone ( J:255349 )

• enlargement of the hypertrophic chondrocyte zone

• however, no changes in the resting and proliferative regions are seen

disorganized long bone epiphyseal plate ( J:255349 )

• E17.5 humeri exhibit a disorganized epiphyseal growth plate and shape

abnormal thoracic cage morphology ( J:255349 )

• the mineralized dorsal aspect of the rib cage is thin and has a wavy appearance

abnormal rib morphology ( J:255349 )

• wavy and thin dorsal ribs at E16.5

abnormal bone marrow cavity morphology ( J:255349 )

• delay in marrow cavity formation, with E17.5 humeri shaft showing an almost complete absence of a marrow cavity

abnormal compact bone morphology ( J:255349 )

• cortical bone formation is severely impaired

absent compact bone ( J:255349 )

• almost total absence of cortical bone in the tibia, with a medullary cavity filled with mineralized material

abnormal trabecular bone morphology ( J:255349 )

• trabecular bone formation is severely impaired

abnormal bone ossification ( J:255349 )

• long bones have little if any cortices and trabeculae and remain cartilaginous such that almost the entire length of the humerus bone is cartilaginous and show a delay in chondrocyte matrix resorption and marrow cavity formation

decreased bone mineralization ( J:255349 )

• reduction of bone mineralization at E14.5 and E18.5, particularly in the mandible and head region

• hypomineralization of the skull bones at E16.5

• calvaria shows a reduction in the mineralization of parietal, frontal, and nasal regions

abnormal intramembranous bone ossification ( J:255349 )

• bones forming through an intramembranous process (mandible and clavicle) are affected

cellular

impaired osteoblast differentiation ( J:255349 )

• severe blunting of osteoblastogenesis, characterized by the persistence of a full unresorbed and mineralized cartilage enlagen throughout the midshaft of long bones

• the bone collar and primary ossification center do not form, suggesting early blunted osteoblast differentiation

abnormal osteoblast physiology ( J:255349 )

• cultured osteoblasts mineralize less than wild-type osteoblasts on day 7 and 14 of culture but are similar to wild-type by day 20

craniofacial

abnormal neurocranium morphology ( J:255349 )

• calvaria shows a reduction in the mineralization of parietal, frontal, and nasal regions

mandible hypoplasia ( J:255349 )

• mandible is hypoplastic and hypomineralized

• however, the mandible Meckel cartilage appears normal

short mandible ( J:255349 )

• mandible is 25-50% shorter

hematopoietic system

abnormal osteoclast morphology ( J:255349 )

• osteoclasts are only present in the restricted wedge-like structure at the midshaft region compared to wild-type where they are abundant throughout the marrow space

homeostasis/metabolism

decreased alkaline phosphatase activity ( J:255349 )

• alkaline phosphatase activity is reduced within the primary spongiosia but is similar along the midshaft presumptive bone cortices

immune system

abnormal osteoclast morphology ( J:255349 )

• osteoclasts are only present in the restricted wedge-like structure at the midshaft region compared to wild-type where they are abundant throughout the marrow space

limbs/digits/tail

abnormal limb morphology ( J:255349 )

• limbs are bent towards the abdomen at E18.5

bowed radius ( J:255349 )

bowed ulna ( J:255349 )

bowed tibia ( J:255349 )

short limbs ( J:255349 )

• forelimbs and hindlimbs are shorter

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	osteogenesis imperfecta type 5	DOID:0110344	OMIM:610967	J:255349