Phenotypes associated with this allele

• Allele Symbol: Fgfr3^tm1Dor
• Allele Name: targeted mutation 1, David M Ornitz
• Allele ID: MGI:1931521
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fgfr3^tm1Dor/Fgfr3^tm1Dor	C3.129S6(B6)-Fgfr3^tm1Dor	MGI:6256787
hm2	Fgfr3^tm1Dor/Fgfr3^tm1Dor	CBACa.129S6(B6)-Fgfr3^tm1Dor	MGI:3696818
hm3	Fgfr3^tm1Dor/Fgfr3^tm1Dor	involves: 129S6/SvEvTac	MGI:3700940
hm4	Fgfr3^tm1Dor/Fgfr3^tm1Dor	involves: 129S6/SvEvTac * C57BL/6	MGI:3589422
cx5	Fgfr3^tm1Dor/Fgfr3^tm1Dor Pthlh^tm1Fbe/Pthlh^tm1Fbe	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ	MGI:3819367
cx6	Fgfr3^tm1Dor/Fgfr3^tm1Dor Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-Fgf9,-EGFP)#Dor/0	involves: 129S6/SvEvTac * C57BL/6J * FVB	MGI:5538522

Genotype
MGI:6256787

hm1

• Allelic Composition: Fgfr3^tm1Dor/Fgfr3^tm1Dor
• Genetic Background: C3.129S6(B6)-Fgfr3^tm1Dor

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

skeleton

abnormal intervertebral disk morphology ( J:244595 )

• intervertebral disk width is decreased on the convex side of apical vertebrae and mice exhibit intervertebral disk compression

• treatment with PTHrP-1-34 inhibits intervertebral disk compression

kyphoscoliosis ( J:244595 )

• mice exhibit a greater mean Cobb angle of thoracic vertebrae beyond 1 month of age that stabilizes around 4 months of age when mice reach skeletal maturity indicating spine curvature

• mice show a sigmoid curvature at 2 months which increases in severity to 4 months indicating progressive scoliosis

• the apical vertebrae shows the maximal lateral displacement and rotation

• mice show a significant rotation of T8 through T12 in the presence of a relatively small lateral displacement of the spine

• continuous release of the bone anabolic peptide parathyroid hormone related protein (PTHrP-1-34) form pellets implanted adjacent to the thoracic spine at 1 month of age inhibits progression of scoliosis, reducing curvature and axial rotation, but does not alter bone volume or the development of kyphosis

abnormal vertebrae morphology ( J:244595 )

• vertebrae show a reduction in trabecular bone

• L5 vertebrae shows a reduction in bone volume/total volume

• apical vertebrae shows reduced bone volume/total volume ratio in the convex side but normal concave side

• overall increase in length of vertebrae and a reduction in height on the concave side of intervertebral disks

decreased bone mineral density ( J:244595 )

• mice develop osteopenia

• treatment with PTHrP-1-34 has no effect on osteopenia development

decreased bone volume ( J:244595 )

• L5 vertebrae shows a reduction in bone volume/total volume ratio

• apical vertebrae shows reduced bone volume/total volume ratio in the convex side but normal concave side

abnormal trabecular bone morphology ( J:244595 )

• vertebrae show a reduction in trabecular bone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
scoliosis		DOID:0060249		J:244595

Genotype
MGI:3696818

hm2

• Allelic Composition: Fgfr3^tm1Dor/Fgfr3^tm1Dor
• Genetic Background: CBACa.129S6(B6)-Fgfr3^tm1Dor

hearing/vestibular/ear

abnormal pillar cell differentiation ( J:117235 )

• at P0, homozygotes display failure of pillar cell differentiation, as shown by lack of separation between inner and outer hair cells

• inner pillar cells never develop while outer pillar cell differentiation is stalled

abnormal cochlear sensory epithelium morphology ( J:117235 )

• homozygotes exhibit an expansion of the sensory epithelium to include one extra OHC row and accompanying Dieters cells

abnormal cochlear hair cell morphology ( J:117235 )

• at 4 weeks, homozygotes lack a well-defined separation between IHCs and OHCs

increased cochlear outer hair cell number ( J:117235 )

• Background Sensitivity: no extra OHC row is noted on a mixed 129S6/SvEvTac x C57BL/6 genetic background

• on a CBA/CaJ congenic background, E17.5 homozygotes on a with an extra row of Dieters cells display an extra fourth row of OHCs in the apical two thirds of the cochlea

• an extra OHC row occurs precisely at the transition from 3 to 4 rows of Dieters cells; however, OHC stereociliary bundle formation and overall cochlear length remain normal

increased Deiters cell number ( J:117235 )

• homozygotes display an additional row of Dieters cells (i.e. 4 rows instead of 3) in the apical two thirds of the cochlea

absent pillar cells ( J:117235 )

• homozygotes show loss of one row of pillar cells throughout the cochlea

absent tunnel of Corti ( J:117235 )

• adult homozygotes show a complete lack of tunnel formation

increased or absent threshold for auditory brainstem response ( J:117235 )

• homozygotes display a 50-60 dB threshold shift across all frequencies

sensorineural hearing loss ( J:117235 )

• homozygotes display a severe hearing loss due to pillar defects

nervous system

abnormal cochlear hair cell morphology ( J:117235 )

• at 4 weeks, homozygotes lack a well-defined separation between IHCs and OHCs

increased cochlear outer hair cell number ( J:117235 )

• Background Sensitivity: no extra OHC row is noted on a mixed 129S6/SvEvTac x C57BL/6 genetic background

• on a CBA/CaJ congenic background, E17.5 homozygotes on a with an extra row of Dieters cells display an extra fourth row of OHCs in the apical two thirds of the cochlea

• an extra OHC row occurs precisely at the transition from 3 to 4 rows of Dieters cells; however, OHC stereociliary bundle formation and overall cochlear length remain normal

cellular

abnormal pillar cell differentiation ( J:117235 )

• at P0, homozygotes display failure of pillar cell differentiation, as shown by lack of separation between inner and outer hair cells

• inner pillar cells never develop while outer pillar cell differentiation is stalled

Genotype
MGI:3700940

hm3

• Allelic Composition: Fgfr3^tm1Dor/Fgfr3^tm1Dor
• Genetic Background: involves: 129S6/SvEvTac

skeleton

long humerus ( J:109505 )

• humerus length of neonates is 3.43 mm versus 2.8 mm in wild-type neonates

long radius ( J:109505 )

• radius length of neonates is 3.8 mm versus 3.04 mm in wild-type neonates

long ulna ( J:109505 )

• ulna is longer in neonates than in controls

long femur ( J:109505 )

• femur length of neonates is 2.78 mm versus 2.46 mm in wild-type neonates

abnormal long bone epiphyseal plate morphology ( J:109505 )

• there is also a slight but significant increase in proliferating cells of the epiphyses (16.5% versus 13.03%)

increased width of hypertrophic chondrocyte zone ( J:109505 )

• depth of both type II and type X collagen immunoreactive cells is increased in the cartilage of the tibial epiphysis of neonates

• there is a disproportionate increase in the depth of type X positive cells that demarcate the hypertrophic zone

abnormal axial skeleton morphology ( J:109505 )

• the axial skeleton is elongated in neonates compared to controls

nervous system

nervous system phenotype ( J:118802 , J:122940 )

N • mutants do not show defects in brain morphology and development (hindbrain patterning, boundary development or neurotransmitter system) (J:118802)

N • mice do not display any defects in motor neuron patterning (J:122940)

limbs/digits/tail

long humerus ( J:109505 )

• humerus length of neonates is 3.43 mm versus 2.8 mm in wild-type neonates

long radius ( J:109505 )

• radius length of neonates is 3.8 mm versus 3.04 mm in wild-type neonates

long ulna ( J:109505 )

• ulna is longer in neonates than in controls

long femur ( J:109505 )

• femur length of neonates is 2.78 mm versus 2.46 mm in wild-type neonates

Genotype
MGI:3589422

hm4

• Allelic Composition: Fgfr3^tm1Dor/Fgfr3^tm1Dor
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

mortality/aging

premature death ( J:32991 )

• mice die at various ages between 1 day and 8 months of age

postnatal lethality, incomplete penetrance ( J:32991 )

• 48% die between birth and 21 days of age

growth/size/body

decreased body weight ( J:32991 )

• weight ranges from 17-93% of that of controls

small thoracic cavity ( J:32991 )

hearing/vestibular/ear

abnormal cochlea morphology ( J:32991 )

• adult cochleas resemble those of normal newborn mice

• the blood vessel below the basilar membrane is patent and numerous mesothelial cells are present below the basilar membrane

abnormal organ of Corti morphology ( J:32991 )

abnormal pillar cell differentiation ( J:32991 )

abnormal cochlear outer hair cell morphology ( J:32991 )

• reduced innervation of outer hair cells

abnormal cochlear OHC efferent innervation pattern ( J:32991 )

increased Deiters cell number ( J:32991 )

• as expected, homozygotes exhibit one row of Deiters' cells beneath each of the 3-4 rows of OHCs

• however, homozygotes also have two rows of "Deiters'-like cells", probably due to failure of these cells to develop into pillar cells

absent pillar cells ( J:32991 )

• no recognizable inner and outer pillar cells between 15 days and 7 months of age

absent tunnel of Corti ( J:32991 )

increased or absent threshold for auditory brainstem response ( J:32991 )

• at 3 weeks to 6 months, homozygotes show no auditory brainstem responses at 100 dB SPL, indicating profound deafness

deafness ( J:32991 )

sensorineural hearing loss ( J:32991 )

skeleton

abnormal long bone morphology ( J:32991 )

abnormal humerus morphology ( J:32991 )

• overgrowth of the humerus in 6 month or older mice

bowed humerus ( J:32991 )

• 75% of 7 week or older mice exhibit increased curvature of the humerus

abnormal femur morphology ( J:32991 )

bowed femur ( J:32991 )

• increased curvature of the femur in 7 week or older mice

long femur ( J:32991 )

• femurs at 4.5 months of age or older are 6-27% longer than controls

abnormal long bone hypertrophic chondrocyte zone ( J:32991 )

• growth plates contain more hypertrophic chondrocytes than controls

increased width of hypertrophic chondrocyte zone ( J:32991 )

• consistent increase in the size of hypertrophic zones

• height of the proximal tibial hypertrophic zone at E18.5 and P1 is increased 33-50%

increased long bone epiphyseal plate size ( J:32991 )

• growth plates of long bones are longer at 3 weeks of age

• acellular bands in growth plates are narrower and less numerous than in controls

abnormal axial skeleton morphology ( J:32991 )

abnormal rib morphology ( J:32991 )

• ribs are abnormally shaped, resulting in a reduction of thoracic cavity volume

kyphosis ( J:32991 )

• primarily in the cervical and upper thoracic spine

• first observed at 1 week after birth and develops in all mice by several months of age

scoliosis ( J:32991 )

• severe scoliosis, primarily in the cervical and upper thoracic spine

enlarged vertebral body ( J:32991 )

• overgrowth of the lumbar vertebral bodies in 6 month old mice

behavior/neurological

absent gastric milk in neonates ( J:32991 )

• several hours after birth, have smaller milk spots, indicating poor nursing

limbs/digits/tail

abnormal humerus morphology ( J:32991 )

• overgrowth of the humerus in 6 month or older mice

bowed humerus ( J:32991 )

• 75% of 7 week or older mice exhibit increased curvature of the humerus

abnormal femur morphology ( J:32991 )

bowed femur ( J:32991 )

• increased curvature of the femur in 7 week or older mice

long femur ( J:32991 )

• femurs at 4.5 months of age or older are 6-27% longer than controls

kinked tail ( J:32991 )

• tail kinks or bends are first observed at P1 and develop in 72% of mice

nervous system

abnormal cochlear outer hair cell morphology ( J:32991 )

• reduced innervation of outer hair cells

abnormal cochlear OHC efferent innervation pattern ( J:32991 )

cellular

abnormal pillar cell differentiation ( J:32991 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	achondroplasia	DOID:4480	OMIM:100800	J:32991

Genotype
MGI:3819367

cx5

• Allelic Composition: Fgfr3^tm1Dor/Fgfr3^tm1Dor; Pthlh^tm1Fbe/Pthlh^tm1Fbe
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ

mortality/aging

neonatal lethality, complete penetrance ( J:109505 )

• neonatal lethality occurs to these mice

skeleton

short humerus ( J:109505 )

• humerus length of neonates is 2.10 mm versus 2.80 mm in wild-type neonates

short radius ( J:109505 )

• radius length of neonates is 2.30 mm versus 3.04 mm in wild-type neonates

short ulna ( J:109505 )

• is observed in neonates compared to controls

short femur ( J:109505 )

• femur length of neonates is 2.14 mm versus 2.46 mm in wild-type neonates

abnormal long bone epiphyseal plate morphology ( J:109505 )

• there is a significant decrease in proliferating cells of the epiphyses (8.74% versus 13.03%)

abnormal long bone hypertrophic chondrocyte zone ( J:109505 )

• larger, irregularly shaped cells are dispersed among the normal, regular shaped hypertrophic cells

• mineral deposits are only observed in the lowermost zones of hyprertrophic cells instead of throughout the hypertrophic zone as is seen in wild-type

increased width of hypertrophic chondrocyte zone ( J:109505 )

• while the epiphyseal cartilage is reduced compared to wild-type, there is a disproportionate increase in the depth of type X positive cells that demarcate the hypertrophic zone

decreased long bone epiphyseal plate size ( J:109505 )

• the total epiphyseal cartilage is considerably reduced compared to controls

abnormal axial skeleton morphology ( J:109505 )

• the axial skeleton is shortened in neonates compared to controls

domed cranium ( J:109505 )

• is observed in these mice

limbs/digits/tail

short humerus ( J:109505 )

• humerus length of neonates is 2.10 mm versus 2.80 mm in wild-type neonates

short radius ( J:109505 )

• radius length of neonates is 2.30 mm versus 3.04 mm in wild-type neonates

short ulna ( J:109505 )

• is observed in neonates compared to controls

short femur ( J:109505 )

• femur length of neonates is 2.14 mm versus 2.46 mm in wild-type neonates

short limbs ( J:109505 )

• is observed in these mice

craniofacial

domed cranium ( J:109505 )

• is observed in these mice

Genotype
MGI:5538522

cx6

• Allelic Composition: Fgfr3^tm1Dor/Fgfr3^tm1Dor; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-Fgf9,-EGFP)#Dor/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB

neoplasm

decreased organ/body region tumor incidence ( J:204282 )

• at 1 week or 1 month of induction with doxycycline, mutants do not exhibit formation of lung tumors and lung histology remains normal