Phenotypes associated with this allele

• Allele Symbol: Ltbp3^tm1Bdvc
• Allele Name: targeted mutation 1, Branka Dabovic
• Allele ID: MGI:2180017
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ltbp3^tm1Bdvc/Ltbp3^tm1Bdvc	involves: 129S6/SvEvTac	MGI:2451201

Genotype
MGI:2451201

hm1

• Allelic Composition: Ltbp3^tm1Bdvc/Ltbp3^tm1Bdvc
• Genetic Background: involves: 129S6/SvEvTac

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

Skeletal abnormalities in Ltbp3^tm1Bdvc/Ltbp3^tm1Bdvc mice

craniofacial

abnormal craniofacial bone morphology ( J:76213 )

abnormal cranium morphology ( J:79920 )

abnormal basicranium morphology ( J:76213 , J:79920 )

• homozygotes fail to extend the presphenoid, basosphenoid, and the basooccipital bones resulting in a shortened cranial base and abnormal incisor apposition (J:76213)

short basicranium ( J:76213 )

• shortened cranial base

abnormal neurocranium morphology ( J:76213 )

• the membranous bones of the mutant vault expand outward and upward, resulting in a domed skull

• no pathological synostosis, i.e. premature fusion of cranial vault sutures is observed

abnormal basioccipital bone morphology ( J:76213 , J:79920 )

• at 1-2 d after birth, homozygotes show abnormal basooccipital-basosphenoid synchondrosis, with no columns of proliferating chondrocytes identified in the mutant synchondrosis (J:76213)

abnormal basisphenoid bone morphology ( J:76213 , J:79920 )

abnormal foramen magnum morphology ( J:76213 )

• the foramen magnum is displaced to a more anterior position

abnormal frontal bone morphology ( J:79920 )

• at 2-, 4 and 12 months, homozygotes fail to exhibit fusion of the frontal bones

occipital bossing ( J:79920 )

• mutant skulls exhibit occipital bossing

misaligned incisors ( J:76213 , J:79920 )

• at 2 months, homozygotes exhibit abnormal apposition of the upper and lower incisors (J:76213)

• lower incisors extend outside of/or abut the upper incisors (J:79920)

abnormal enamel organ morphology ( J:220985 )

• analysis of continuously growing incisor enamel organ shows a cohesive, however at defined locations, non-palisadic ameloblast layer facing a thinner disorganized enamel matrix

abnormal enamel morphology ( J:220985 )

• enamel is less mineralized and exhibits an unusual wavy pattern with alternating area of presence/absence

reduced enamel thickness ( J:220985 )

• enamel defects with very thin or absent enamel in both incisors and molars

malocclusion ( J:76213 , J:79920 )

• at 2 months, the mutant mandible extends beyond the maxilla (J:76213)

• shortening of the cranial base disrupts the normal closure of the upper and lower jaws (J:79920)

short maxilla ( J:79920 , J:220985 )

prognathia ( J:220985 )

• mandibular prognathism

domed cranium ( J:76213 , J:79920 )

• at 2 months, homozygotes exhibit a domed skull (J:76213)

ectopic cranial bone ( J:76213 )

short snout ( J:76213 , J:79920 )

• by day 10, homozygotes display a shortened snout (J:76213)

round head ( J:76213 )

• homozygotes are born in the expected Mendelian ratio with no overt defects; however, at day 10, mutants exhibit a rounded head

growth/size/body

misaligned incisors ( J:76213 , J:79920 )

• at 2 months, homozygotes exhibit abnormal apposition of the upper and lower incisors (J:76213)

• lower incisors extend outside of/or abut the upper incisors (J:79920)

abnormal enamel organ morphology ( J:220985 )

• analysis of continuously growing incisor enamel organ shows a cohesive, however at defined locations, non-palisadic ameloblast layer facing a thinner disorganized enamel matrix

abnormal enamel morphology ( J:220985 )

• enamel is less mineralized and exhibits an unusual wavy pattern with alternating area of presence/absence

reduced enamel thickness ( J:220985 )

• enamel defects with very thin or absent enamel in both incisors and molars

malocclusion ( J:76213 , J:79920 )

• at 2 months, the mutant mandible extends beyond the maxilla (J:76213)

• shortening of the cranial base disrupts the normal closure of the upper and lower jaws (J:79920)

short snout ( J:76213 , J:79920 )

• by day 10, homozygotes display a shortened snout (J:76213)

round head ( J:76213 )

• homozygotes are born in the expected Mendelian ratio with no overt defects; however, at day 10, mutants exhibit a rounded head

decreased body weight ( J:76213 , J:79920 )

• at 3 months, homozygotes weigh less than 60% of wild-type and heterozygous sex-matched littermates (J:76213)

• by 8 days, homozygotes weigh 70-80% of wild-type and heterozygous sex-matched littermates (J:79920)

• at 3 weeks, homozygotes weigh 30-80% of wild-type and heterozygous littermates (J:79920)

postnatal growth retardation ( J:76213 )

• by day 8 after birth, homozygotes exhibit growth retardation

immune system

osteoarthritis ( J:76213 , J:79920 )

• at 6-9 months, homozygotes develop progressive degeneration of articular cartilage resembling osteoarthritis (J:76213)

• by 9 months, homozygotes show absence of articular cartilage; the articular surface looks ossified and fibrotic and osteophytes are present (J:76213)

skeleton

abnormal craniofacial bone morphology ( J:76213 )

abnormal cranium morphology ( J:79920 )

abnormal basicranium morphology ( J:76213 , J:79920 )

• homozygotes fail to extend the presphenoid, basosphenoid, and the basooccipital bones resulting in a shortened cranial base and abnormal incisor apposition (J:76213)

short basicranium ( J:76213 )

• shortened cranial base

abnormal neurocranium morphology ( J:76213 )

• the membranous bones of the mutant vault expand outward and upward, resulting in a domed skull

• no pathological synostosis, i.e. premature fusion of cranial vault sutures is observed

abnormal basioccipital bone morphology ( J:76213 , J:79920 )

• at 1-2 d after birth, homozygotes show abnormal basooccipital-basosphenoid synchondrosis, with no columns of proliferating chondrocytes identified in the mutant synchondrosis (J:76213)

abnormal basisphenoid bone morphology ( J:76213 , J:79920 )

abnormal foramen magnum morphology ( J:76213 )

• the foramen magnum is displaced to a more anterior position

abnormal frontal bone morphology ( J:79920 )

• at 2-, 4 and 12 months, homozygotes fail to exhibit fusion of the frontal bones

occipital bossing ( J:79920 )

• mutant skulls exhibit occipital bossing

misaligned incisors ( J:76213 , J:79920 )

• at 2 months, homozygotes exhibit abnormal apposition of the upper and lower incisors (J:76213)

• lower incisors extend outside of/or abut the upper incisors (J:79920)

abnormal enamel organ morphology ( J:220985 )

• analysis of continuously growing incisor enamel organ shows a cohesive, however at defined locations, non-palisadic ameloblast layer facing a thinner disorganized enamel matrix

abnormal enamel morphology ( J:220985 )

• enamel is less mineralized and exhibits an unusual wavy pattern with alternating area of presence/absence

reduced enamel thickness ( J:220985 )

• enamel defects with very thin or absent enamel in both incisors and molars

malocclusion ( J:76213 , J:79920 )

• at 2 months, the mutant mandible extends beyond the maxilla (J:76213)

• shortening of the cranial base disrupts the normal closure of the upper and lower jaws (J:79920)

short maxilla ( J:79920 , J:220985 )

prognathia ( J:220985 )

• mandibular prognathism

domed cranium ( J:76213 , J:79920 )

• at 2 months, homozygotes exhibit a domed skull (J:76213)

ectopic cranial bone ( J:76213 )

osteoarthritis ( J:76213 , J:79920 )

• at 6-9 months, homozygotes develop progressive degeneration of articular cartilage resembling osteoarthritis (J:76213)

• by 9 months, homozygotes show absence of articular cartilage; the articular surface looks ossified and fibrotic and osteophytes are present (J:76213)

abnormal long bone epiphyseal plate proliferative zone ( J:76213 , J:79920 , J:163721 )

• at 1-2 d after birth, homozygotes show no identifiable columns of proliferating chondrocytes in the basooccipital-basosphenoid synchondrosis (J:76213)

• cell density in the proliferative zone is increased compared to in wild-type mice (J:163721)

increased width of hypertrophic chondrocyte zone ( J:76213 , J:79920 , J:163721 )

• at 1-2 d after birth, homozygotes exhibit wider zones of hypertrophic chondrocytes in the basooccipital-basosphenoid synchondrosis (J:76213)

abnormal long bone metaphysis morphology ( J:76213 )

• at 6-9 months, homozygotes show an increased number of metaphysial trabeculae in long bones and vertebrae

decreased length of long bones ( J:76213 , J:79920 )

• endochondral bones from adult homozygotes are shorter by ~10-25% relative to wild-type (J:76213)

abnormal thoracic cage shape ( J:79920 )

• homozygotes exhibit a distorted ribcage

abnormal thoracic vertebrae morphology ( J:76213 , J:79920 )

• at 2 months, homozygotes display curvature of the thoracic vertebrae (J:76213)

kyphosis ( J:76213 , J:79920 )

• at 2 months, homozygotes show thoracic kyphosis (J:76213)

abnormal cervical vertebrae morphology ( J:76213 , J:79920 )

• at 2 months, homozygotes display curvature of the cervical vertebrae (J:76213)

abnormal trabecular bone morphology ( J:79920 )

increased trabecular bone mass ( J:76213 )

• at 3 months, homozygotes exhibit increased trabecular mass in the long bones and vertebrae

osteosclerosis ( J:76213 , J:79920 )

• homozygotes develop progressive osteosclerosis between 6 and 9 months of age (J:76213)

abnormal joint morphology ( J:76213 )

• at 6-9 months, mutant knee and vertebral joints show degenerative changes in articular cartilage

premature bone ossification ( J:76213 , J:79920 )

• within 2 weeks of birth, mutant skulls exhibit premature ossification of the cranial base synchondroses; in contrast, wild-type synchondroses never ossify, enabling growth of the cranial base through endochondral ossification (J:76213)

abnormal bone remodeling ( J:76213 , J:79920 )

• homozygotes defective bone remodeling and homeostasis, consistent with aberrant TGF-beta signaling in the skull and long bones (J:76213)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
brachyolmia-amelogenesis imperfecta syndrome		DOID:0090143	OMIM:601216	J:220985