Phenotypes Associated with This Genotype

Genotype
MGI:6416454

• Allelic Composition: Fgfr3^{tm1.1(FGFR3*)Ytc}/Fgfr3^{tm1.1(FGFR3*)Ytc}
• Genetic Background: involves: 129

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

mortality/aging

decreased survivor rate ( J:287271 )

premature death ( J:287271 )

• majority of mice die at around 1 year of age

neonatal lethality, incomplete penetrance ( J:287271 )

• lower survival rate at birth

postnatal lethality, incomplete penetrance ( J:287271 )

• higher mortality rate before 4 weeks of age

growth/size/body

misaligned incisors ( J:287271 )

• protrusion of the lower incisors because of changes in the skull

midface hypoplasia ( J:287271 )

short snout ( J:287271 )

• short snout is seen at 10 days to 1 month of age

round head ( J:287271 )

• rounded head is seen at 10 days to 1 month of age

decreased body weight ( J:287271 )

decreased body length ( J:287271 )

disproportionate dwarf ( J:287271 )

• dwarfism phenotypes become gradually evident in mice; limbs are disproportionately shortened relative to body length

skeleton

decreased chondrocyte proliferation ( J:287271 )

• primary chondrocytes show lower proliferation rates

abnormal cranium morphology ( J:287271 )

• skull is rounded in newborns

absent jugum limitans ( J:287271 )

• the jugum limitans, the cranial suture that separates the frontal and nasal bones, is absent

abnormal neurocranium morphology ( J:287271 )

• calvarial bones are distorted due to a positional shift and compression of the frontal and parietal bones

misaligned incisors ( J:287271 )

• protrusion of the lower incisors because of changes in the skull

domed cranium ( J:287271 )

decreased osteoclast cell number ( J:287271 )

• fewer osteoclasts in femurs at 1 year of age

bowed femur ( J:287271 )

short femur ( J:287271 )

• femur length is reduced 42% in newborns

increased diameter of femur ( J:287271 )

• femurs are thick

abnormal long bone diaphysis morphology ( J:287271 )

• femurs show widened diaphysis

abnormal long bone epiphyseal plate morphology ( J:287271 )

• reduction in the number of proliferative chondrocytes

• arrangement of chondrocyte columns is disturbed with an increased amount of space between the columns at 4 and 8 weeks of age

• however, the arrangement of chondrocyte columns in the growth plate remains normal before 2 weeks of age and epiphyseal structure is normal at birth

abnormal long bone epiphyseal plate proliferative zone ( J:287271 )

• growth plates are shorter, with a shorter proliferative zone at 2, 4, and 8 weeks of age

abnormal long bone hypertrophic chondrocyte zone ( J:287271 )

• osteocalcin expression which is associated with early stages of matrix ossification is increased in chondrocytes of the hypertrophic zone of the distal femur at 2 weeks of age

decreased width of hypertrophic chondrocyte zone ( J:287271 )

• reduction in hypertrophic zone at 8 weeks of age

decreased long bone epiphyseal plate size ( J:287271 )

abnormal long bone metaphysis morphology ( J:287271 )

• femurs show flared metphyses

• distal femoral metaphysis shows lower bone volume

• reduction in the growth of the longitudinal trabecular bone in the distal femoral metaphysis is seen at several postnatal development stages

abnormal thoracic cage morphology ( J:287271 )

• narrower rib cage

abnormal vertebral column morphology ( J:287271 )

• shorter intervertebral distance between cervical vertebrae

kyphosis ( J:287271 )

• mice develop kyphosis at around 2 weeks of age

• severe curvature of the cervical and upper thoracic vertebrae, with almost completely folded upper thoracic vertebrae

decreased bone mineral density ( J:287271 )

• low bone density at birth, in adolescent and adult

decreased bone volume ( J:287271 )

• distal femoral metaphysis shows lower bone volume

decreased trabecular bone volume ( J:287271 )

• trabecular bone volume is decreased in distal femur metaphysis at birth and 1 year of age

decreased osteoblast cell number ( J:287271 )

• fewer osteoblasts in femurs at 1 year of age

decreased bone trabecula number ( J:287271 )

• trabecular number is decreased in distal femur metaphysis at birth and 1 year of age

increased bone trabecular spacing ( J:287271 )

• trabecular separation is increased in distal femur metaphysis at birth and 1 year of age

decreased trabecular bone thickness ( J:287271 )

• trabecular thickness is decreased in distal femur metaphysis at birth and 1 year of age

abnormal bone ossification ( J:287271 )

• bone-forming process is disturbed

• the fewer osteoblasts and osteoclasts in femurs suggests that bone turnover rate is altered

premature craniofacial suture closure ( J:287271 )

• newborns show premature suture closure

premature metopic suture closure ( J:287271 )

• the metopic sutures are unilaterally fused or partially absent

delayed bone ossification ( J:287271 )

• formation of the secondary ossification center is delayed

craniofacial

abnormal cranium morphology ( J:287271 )

• skull is rounded in newborns

absent jugum limitans ( J:287271 )

• the jugum limitans, the cranial suture that separates the frontal and nasal bones, is absent

abnormal neurocranium morphology ( J:287271 )

• calvarial bones are distorted due to a positional shift and compression of the frontal and parietal bones

misaligned incisors ( J:287271 )

• protrusion of the lower incisors because of changes in the skull

domed cranium ( J:287271 )

midface hypoplasia ( J:287271 )

short snout ( J:287271 )

• short snout is seen at 10 days to 1 month of age

round head ( J:287271 )

• rounded head is seen at 10 days to 1 month of age

cellular

decreased chondrocyte proliferation ( J:287271 )

• primary chondrocytes show lower proliferation rates

hematopoietic system

decreased osteoclast cell number ( J:287271 )

• fewer osteoclasts in femurs at 1 year of age

immune system

decreased osteoclast cell number ( J:287271 )

• fewer osteoclasts in femurs at 1 year of age

limbs/digits/tail

bowed femur ( J:287271 )

short femur ( J:287271 )

• femur length is reduced 42% in newborns

increased diameter of femur ( J:287271 )

• femurs are thick

rhizomelic limb ( J:287271 )

• newborns show proximal limb shortening with relatively normally sized trunks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
achondroplasia		DOID:4480	OMIM:100800	J:287271