Phenotypes Associated with This Genotype

Genotype
MGI:7517089

• Allelic Composition: Fgfr3^tm3.1Llm/Fgfr3⁺
• Genetic Background: involves: C57BL/6N

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

growth/size/body

decreased body size ( J:338859 )

• mice exhibit a progressive dwarfism from birth and throughout adulthood

decreased body weight ( J:338859 )

• body weight is decreased, with a 35% reduction in weight at P60

decreased body length ( J:338859 )

• naso-anal length is similar to control on P7 but is reduced by 12% on P21, 14% on P60, and 9% on P180

craniofacial

abnormal cranium morphology ( J:338859 )

• mice exhibit abnormal skull morphology on P14

• mice show a more globular skull shape, with increased width and reduced length

abnormal foramen magnum morphology ( J:338859 )

• foramen magnum shape is abnormal and the foramen magnum area is decreased by 19%

short basicranium ( J:338859 )

• skull base length is decreased by 21%

premature cranial synchondrosis closure ( J:338859 )

• sphenooccipital synchondroses and intrasphenoidal synchondrosis fusion and partial fusion of the intra-occipital synchondroses on P14, whereas synchondroses are patent in controls

premature sphenooccipital synchondrosis closure ( J:338859 )

• spheno-occipital synchondroses are seen at P14, whereas synchondroses are patent in controls

decreased cranium length ( J:338859 )

increased cranium width ( J:338859 )

prognathia ( J:338859 )

• the mandible is prognathic

• the intercondylar and intergonial distances are relatively wide compared with controls

domed cranium ( J:338859 )

• mice exhibit a dome-shaped skull, with reduced length, increased width, and decreased centroid size

skeleton

abnormal skeleton morphology ( J:338859 )

• progressive skeletal phenotype from P7 until P180

abnormal cranium morphology ( J:338859 )

• mice exhibit abnormal skull morphology on P14

• mice show a more globular skull shape, with increased width and reduced length

abnormal foramen magnum morphology ( J:338859 )

• foramen magnum shape is abnormal and the foramen magnum area is decreased by 19%

short basicranium ( J:338859 )

• skull base length is decreased by 21%

premature cranial synchondrosis closure ( J:338859 )

• sphenooccipital synchondroses and intrasphenoidal synchondrosis fusion and partial fusion of the intra-occipital synchondroses on P14, whereas synchondroses are patent in controls

premature sphenooccipital synchondrosis closure ( J:338859 )

• spheno-occipital synchondroses are seen at P14, whereas synchondroses are patent in controls

decreased cranium length ( J:338859 )

increased cranium width ( J:338859 )

prognathia ( J:338859 )

• the mandible is prognathic

• the intercondylar and intergonial distances are relatively wide compared with controls

domed cranium ( J:338859 )

• mice exhibit a dome-shaped skull, with reduced length, increased width, and decreased centroid size

abnormal long bone epiphyseal ossification zone morphology ( J:338859 )

• the growth plate shows delayed secondary ossification enter formation at P14

• 43% reduction in secondary ossification center volume per epiphyseal volume at P14

decreased width of hypertrophic chondrocyte zone ( J:338859 )

• hypertrophic zone width is reduced at P14 and P21, with smaller hypertrophic chondrocytes due to a lack of cell swelling

• however, chondrocyte proliferation does not differ at P14 or P21

disorganized long bone epiphyseal plate ( J:338859 )

• while no obvious difference in epiphyseal growth plate structures of the femur is seen at P7, progressive disorganization of the growth plate is seen at P14 and P21, characterized by reduced hypertrophic zone width and delayed secondary ossification center formation at P14

decreased length of long bones ( J:338859 )

• length of long bones is reduced across all analyzed time points, with the largest difference at P60

short femur ( J:338859 )

• reduction in femur length at birth

short tibia ( J:338859 )

• reduction in tibia length at birth

abnormal annulus fibrosus morphology ( J:338859 )

• L5-L6 vertebrae show intervertebral disc deformation with reversed herniation of the inner annulus fibrosus into the nucleus pulposus region

abnormal vertebrae morphology ( J:338859 )

• mice exhibit reduced vertebral bone mass and strength

abnormal vertebral body morphology ( J:338859 )

• 12% reduction in vertebral body length, 8% reduction in interpedicular distance and 14% reduction in the canal area of the fifth lumbar in 10-week-old male mice

short vertebral body ( J:338859 )

• 12% reduction in length of the fifth lumbar vertebral body in 10-week-old mice

decreased bone mineral density of vertebrae ( J:338859 )

• 7% reduction in bone mineral density of vertebrae

decreased bone volume ( J:338859 )

• 18% reduction in bone volume per tissue volume of vertebrae

• femurs and tibiae show a 30-42% and 24-38% reduction, respectively, in bone volume to tissue volume ratio at P42, P70, and P180

abnormal compact bone morphology ( J:338859 )

• femurs and tibiae show a decrease in total cortical diameter at P42, P70, and P180

• femoral bone shows a 6-10% increase in cortical bone mineral density at P42, P70, and P180

• -tibiae shows a 6% increase in cortical bone mineral density only at P180

increased compact bone volume ( J:338859 )

• femurs and tibiae show an increase in cortical bone volume to tissue volume at P180

abnormal compact bone lamellar structure ( J:338859 )

• femur mid-shaft cortical bone from P180 males shows a 40% decrease in cortical microporosity, 29% decrease in lacunae number per bone volume and 16% decrease in median lacunae volume

• femur mid-shaft cortical bone from P180 males shows a higher percentage of small lacunae and a lower percentage of large lacunae and increased lacuna shape sphericity

increased compact bone thickness ( J:338859 )

• femurs and tibiae show an increase in the ratio of the cortical thickness to the total diameter on P180

abnormal trabecular bone morphology ( J:338859 )

• femurs show a 4% decrease in trabecular bone mineral density on P70

decreased bone trabecula number ( J:338859 )

• femurs show a 10-17% decrease in trabecular number at P42, P70, and P180

• tibiae show a similar decrease in trabecular number as femurs at P70 and P180, but not at P42

increased bone trabecular spacing ( J:338859 )

• femurs show a 12-28% increase in trabecular space at P42, P70, and P180

• tibiae show a similar increase in trabecular space as femurs at P70 and P180, but not at P42

decreased trabecular bone thickness ( J:338859 )

• 15% decrease in trabecular thickness of vertebrae

• femurs and tibiae show a 13-17% and 7-15% decrease, respectively, in trabecular thickness at P70 and P180

abnormal chondrocyte differentiation ( J:338859 )

• marker analysis indicates impaired chondrocyte differentiation in the growth plate

abnormal endochondral bone ossification ( J:338859 )

• mice exhibit abnormal endochondral ossification that results in premature fusion of the skull synchondroses, leading to multiple craniofacial anomalies

decreased bone stiffness ( J:338859 )

• long bones show 37-53% reduced stiffness at P42, P70, and P180 in 3-point bend testing

decreased vertebra stiffness ( J:338859 )

• lumbar vertebrae show a 34% decrease in stiffness

decreased bone strength ( J:338859 )

• long bones show reduced strength

• long bones show 21% reduced plastic work to total work at P180

decreased femur maximal load ( J:338859 )

• long bones show 24-37% reduced maximal load at P42, P70, and P180 in 3-point bend testing

decreased femur yield load ( J:338859 )

• long bones show 18-28% reduced yield load at P42, P70, and P180 in 3-point bend testing

decreased vertebra maximal load ( J:338859 )

• lumbar vertebrae show a 22% reduction in maximal load

decreased energy dissipated prior to femur fracture ( J:338859 )

• long bones show 37% reduced toughness (energy dissipated at fracture) at P180

fragile skeleton ( J:338859 )

• in older mice, the increased cortical thickness and mineralization results in reduced toughness and a brittle phenotype

limbs/digits/tail

short femur ( J:338859 )

• reduction in femur length at birth

short tibia ( J:338859 )

• reduction in tibia length at birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypochondroplasia		DOID:0080041	OMIM:146000	J:338859