Phenotypes associated with this allele

• Allele Symbol: Fgfr3^tm1Led
• Allele Name: targeted mutation 1, Phillip Leder
• Allele ID: MGI:2135634
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fgfr3^tm1Led/Fgfr3^tm1Led	involves: 129S6/SvEvTac	MGI:3640392
cx2	Fgfr3^tm1Led/Fgfr3^tm1Led Glg1^tm1Brle/Glg1^tm1Brle	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J	MGI:4829779
cx3	Fgfr3^tm1Led/Fgfr3^tm1Led Fgfr4^tm1Cxd/Fgfr4^tm1Cxd	involves: 129S6/SvEvTac * Black Swiss	MGI:3653045

Genotype
MGI:3640392

hm1

• Allelic Composition: Fgfr3^tm1Led/Fgfr3^tm1Led
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

lethality at weaning, incomplete penetrance ( J:32105 )

• most severely affected mutants often die around weaning

growth/size/body

decreased body size ( J:32105 )

• most severely affected mutants are usually runted

respiratory system

respiratory distress ( J:32105 )

• most severely affected mutants have breathing difficulties

skeleton

increased osteoclast cell number ( J:32105 )

• increase in the numbers of osteoclasts occupying the growth plate

abnormal long bone morphology ( J:32105 )

long humerus ( J:32105 )

• humeri are elongated

abnormal femur morphology ( J:32105 )

• femurs are bowed, longer, and thicker than in controls

large femur head ( J:32105 )

• heads of femurs are larger than in controls

bowed femur ( J:32105 )

increased diameter of femur ( J:32105 )

long femur ( J:32105 )

• femurs are about 20% and 40% longer than controls at P90-100 and P180-P210, respectively

abnormal fibula morphology ( J:32105 )

• heads of the fibula are larger

abnormal tibia morphology ( J:32105 )

• heads of the tibia are larger

abnormal axial skeleton morphology ( J:32105 )

• overgrowth of the axial skeleton

abnormal spine curvature ( J:32105 )

kyphosis ( J:32105 )

• kyphosis is apparent at P7 and becomes more severe as mutants age

• kyphosis is caused by bending of the vertebral column, generally at the 4th-6th cervical and the 12th-13th thoracic vertebrae

scoliosis ( J:32105 )

• about half develop scoliosis of varying degrees by the time they reach three months of age

kyphoscoliosis ( J:32105 )

• seen in about 10% of younger mutants

abnormal vertebrae morphology ( J:32105 )

• height of the cartilaginous zone of vertebrae is increased

abnormal thoracic vertebrae morphology ( J:32105 )

• thoracic vertebrae are longer than in controls

abnormal vertebral epiphyseal plate morphology ( J:32105 )

• beginning at P4, growth plates of the vertebrae are thicker

elongated vertebral body ( J:32105 )

• vertebral bodies are longer

abnormal epiphyseal plate morphology ( J:32105 )

abnormal long bone epiphyseal plate proliferative zone ( J:32105 )

• increase in the numbers of proliferating chondrocytes in epiphyseal growth plates

abnormal long bone hypertrophic chondrocyte zone ( J:32105 )

• hypertrophic chondrocytes continue to be produced in the expanded growth plates at 6 months of age, a time when there are few hypertrophic chondrocytes in controls

increased width of hypertrophic chondrocyte zone ( J:32105 )

• exhibit expansion of the hypertrophic chondrocyte zone in the growth plates of vertebrae and knee joint (femur and tibia)

increased long bone epiphyseal plate size ( J:32105 )

• expanded in the tibia and femur beginning around 2 months of age

increased bone ossification ( J:32105 )

• increased osteogenesis; enhanced and prolonged endochondrial bone growth

behavior/neurological

abnormal gait ( J:32105 )

• 2-3 months after birth, begin to show a swaying gait abnormality and gradually become bowlegged

limbs/digits/tail

long humerus ( J:32105 )

• humeri are elongated

abnormal femur morphology ( J:32105 )

• femurs are bowed, longer, and thicker than in controls

large femur head ( J:32105 )

• heads of femurs are larger than in controls

bowed femur ( J:32105 )

increased diameter of femur ( J:32105 )

long femur ( J:32105 )

• femurs are about 20% and 40% longer than controls at P90-100 and P180-P210, respectively

abnormal fibula morphology ( J:32105 )

• heads of the fibula are larger

abnormal tibia morphology ( J:32105 )

• heads of the tibia are larger

abnormal tail morphology ( J:32105 )

• by P3, all mutants have tail abnormalities

long tail ( J:32105 )

• after the first 2 weeks of life, tails seem to grow consistently faster than in controls such that by P15, tails are longer

wavy tail ( J:32105 )

• about half develop tail distortions (wavy tail) by P2

hematopoietic system

increased osteoclast cell number ( J:32105 )

• increase in the numbers of osteoclasts occupying the growth plate

immune system

increased osteoclast cell number ( J:32105 )

• increase in the numbers of osteoclasts occupying the growth plate

Genotype
MGI:4829779

cx2

• Allelic Composition: Fgfr3^tm1Led/Fgfr3^tm1Led; Glg1^tm1Brle/Glg1^tm1Brle
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J

skeleton

decreased long bone epiphyseal plate size ( J:163721 )

• mice exhibit decreased growth plates in the femur affecting both the proliferative and hypertrophic compared to in wild-type mice

growth/size/body

decreased body size ( J:163721 )

• at 4 weeks

Genotype
MGI:3653045

cx3

• Allelic Composition: Fgfr3^tm1Led/Fgfr3^tm1Led; Fgfr4^tm1Cxd/Fgfr4^tm1Cxd
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss

mortality/aging

premature death ( J:50677 )

• double homozygotes usually die within the first few months of life

• no double homozygotes survive beyond ~8 months

respiratory system

impaired lung alveolus development ( J:50677 )

• although morphologically normal at P2, double mutant lungs fail to undergo secondary septation to delineate alveoli at P9 and retain a simplified, immature lung parenchyma architecture with abnormally smooth airway walls at P21

• however, no differences in surfactant protein production, cellular proliferation or apoptosis are observed

absent pulmonary alveoli ( J:50677 )

• double mutant lungs lack identifiable alveoli

emphysema ( J:50677 )

• although outwardly normal, double mutant lungs are histologically emphysematous with a ~3-fold enlargement of the air spaces

abnormal pulmonary elastic fiber morphology ( J:50677 )

• starting at ~P21 (i.e. after alveogenesis), double mutant lungs exhibit significantly increased levels of elastin deposition relative to control lungs

• however, no differences in elastin deposition or elastin fiber morphology are observed before or during alveogenesis

growth/size/body

decreased body size ( J:50677 )

• at weaning, double homozygotes are ~50% the size of control siblings, despite an apparently normal birth size

postnatal growth retardation ( J:50677 )

• double homozygotes exhibit significant postnatal growth retardation relative to control siblings

reproductive system

infertility ( J:50677 )

• double homozygotes are largely infertile, although a few are able to produce progeny

homeostasis/metabolism

dehydration ( J:50677 )

• double homozygotes appear sickly and dehydrated

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lower respiratory tract disease		DOID:0050161		J:50677