Phenotypes Associated with This Genotype

Genotype
MGI:3840080

• Allelic Composition: Fgfr3^tm1Llm/Fgfr3⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

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

mortality/aging

premature death ( J:147208 )

• mice die 6 to 8 weeks after birth

skeleton

abnormal skeleton morphology ( J:147208 )

• at P0, mice exhibit skeletal dysplasia that worsens with age unlike wild-type mice

abnormal foramen magnum morphology ( J:147208 )

• mice exhibit anterior displacement of the foramen magnum

short basicranium ( J:147208 )

• the skull base is shortened compared to in wild-type mice

decreased cranium height ( J:147208 )

• with a slight increase in left-right and dorsal-ventral axes

abnormal temporal bone morphology ( J:147208 )

• mice exhibit an abnormal temporal bone orientation

• the region of the temporal bone corresponding to the human mastoid is poorly developed with low pneumatization compared to in wild-type mice

prognathia ( J:147208 )

• prognathic mandible

domed cranium ( J:147208 )

abnormal middle ear ossicle morphology ( J:147208 )

• delayed ossification at P14

abnormal incus morphology ( J:147208 )

• delayed ossification

abnormal malleus morphology ( J:147208 )

• at P7, the orbibular apophysis of the malleus is still cartilaginous unlike in wild-type mice

abnormal stapes morphology ( J:147208 )

• delayed ossification

bowed radius ( J:147208 )

• at 3 weeks of age

bowed ulna ( J:147208 )

• at 3 weeks of age

bowed fibula ( J:147208 )

• at 3 weeks of age

bowed tibia ( J:147208 )

• at 3 weeks of age

small caudal vertebrae ( J:147208 )

decreased length of long bones ( J:147208 )

short femur ( J:147208 )

short ribs ( J:147208 )

decreased chondrocyte number ( J:147208 )

• hypertrophic chondrocytes are reduced in number and size compared to in wild-type mice

abnormal epiphyseal plate morphology ( J:147208 )

• disorganized with shortened chondrocyte columns and hypertrophic chondrocytes that are reduced in number and size

hearing/vestibular/ear

abnormal middle ear ossicle morphology ( J:147208 )

• delayed ossification at P14

abnormal incus morphology ( J:147208 )

• delayed ossification

abnormal malleus morphology ( J:147208 )

• at P7, the orbibular apophysis of the malleus is still cartilaginous unlike in wild-type mice

abnormal stapes morphology ( J:147208 )

• delayed ossification

abnormal cochlea morphology ( J:147208 )

• at P0, ossification in the cochlea is severely delayed compared to in wild-type mice

abnormal organ of Corti morphology ( J:147208 )

• the tunnel of the Corti presents a smaller opening than in wild-type mice

abnormal cochlear outer hair cell morphology ( J:147208 )

• the space in between the outer hair cells is broader than in wild-type mice

• the two first rows of outer hair cells are not supported at their basal poles by Dieter's cell but are replaced by a pillar-like structure called modified Dieter's cells

abnormal Deiters cell morphology ( J:147208 )

• mice exhibit two ectopic pillars (modified Deiter's cells) close to the first two outer hair cells in addition to the two normal pillar cells and instead of normally placed Dieter cells

increased or absent threshold for auditory brainstem response ( J:147208 )

• mice display a significantly higher ABR threshold for frequencies between 3 to 50 kHz, with a maximum of 50 dB for the medium range frequencies, and around 30 dB for lower and higher frequencies indicating a mild hearing loss

deafness ( J:147208 )

craniofacial

abnormal foramen magnum morphology ( J:147208 )

• mice exhibit anterior displacement of the foramen magnum

short basicranium ( J:147208 )

• the skull base is shortened compared to in wild-type mice

decreased cranium height ( J:147208 )

• with a slight increase in left-right and dorsal-ventral axes

abnormal temporal bone morphology ( J:147208 )

• mice exhibit an abnormal temporal bone orientation

• the region of the temporal bone corresponding to the human mastoid is poorly developed with low pneumatization compared to in wild-type mice

prognathia ( J:147208 )

• prognathic mandible

domed cranium ( J:147208 )

abnormal middle ear ossicle morphology ( J:147208 )

• delayed ossification at P14

abnormal incus morphology ( J:147208 )

• delayed ossification

abnormal malleus morphology ( J:147208 )

• at P7, the orbibular apophysis of the malleus is still cartilaginous unlike in wild-type mice

abnormal stapes morphology ( J:147208 )

• delayed ossification

midface hypoplasia ( J:147208 )

• the midface is hypoplastic compared to in wild-type mice

growth/size/body

midface hypoplasia ( J:147208 )

• the midface is hypoplastic compared to in wild-type mice

megacephaly ( J:147208 )

decreased body length ( J:147208 )

nervous system

abnormal cochlear outer hair cell morphology ( J:147208 )

• the space in between the outer hair cells is broader than in wild-type mice

• the two first rows of outer hair cells are not supported at their basal poles by Dieter's cell but are replaced by a pillar-like structure called modified Dieter's cells

limbs/digits/tail

bowed radius ( J:147208 )

• at 3 weeks of age

bowed ulna ( J:147208 )

• at 3 weeks of age

short femur ( J:147208 )

bowed fibula ( J:147208 )

• at 3 weeks of age

bowed tibia ( J:147208 )

• at 3 weeks of age

small caudal vertebrae ( J:147208 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thanatophoric dysplasia		DOID:13481	OMIM:187600 OMIM:187601 OMIM:273680	J:147208