Phenotypes associated with this allele

• Allele Symbol: Fgfr3^em1.1Ntsu
• Allele Name: endonuclease-mediated mutation 1.1, Noriyuki Tsumaki
• Allele ID: MGI:8403692
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Fgfr3^em1.1Ntsu/Fgfr3^+	C57BL/6-Fgfr3^em1.1Ntsu	MGI:8404456
cn2	Fgfr3^em1.1Ntsu/Fgfr3^+ Gt(ROSA)26Sor^tm1(CAG-Brainbow2.1)Cle/Gt(ROSA)26Sor^+ Tg(Col11a2-cre/ERT)#Ntsu/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JJcl * C57BL/6NSlc	MGI:8404486

Genotype
MGI:8404456

ht1

• Allelic Composition: Fgfr3^em1.1Ntsu/Fgfr3⁺
• Genetic Background: C57BL/6-Fgfr3^em1.1Ntsu

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

mortality/aging

premature death ( J:390604 )

• 85% of mice die by P36

growth/size/body

misaligned incisors ( J:390604 )

• incisors do not align normally because of changes in the skull

decreased body size ( J:390604 )

• mice develop dwarfism

decreased body weight ( J:390604 )

• both males and females show decreased body weight as they age

• mice administered the CREB inhibitor 666-15 from P7 to P27 exhibit partially restored weight

skeleton

decreased chondrocyte proliferation ( J:390604 )

• the proliferative zone height is decreased at P21, P24, and P28, suggesting inhibition of chondrocyte proliferation

misaligned incisors ( J:390604 )

• incisors do not align normally because of changes in the skull

abnormal long bone epiphyseal plate morphology ( J:390604 )

• the height of the resting zone is slightly increased at P18, and the expansion of the resting zone becomes remarkable at P21

• the expanded resting zone contains limited amounts of proteoglycan and type II collagen and because the secondary ossification center is formed at P18, this expanded resting zone is not simply residual epiphyseal cartilage

• a number of cells in the expanded resting zone at P4-7 undergo slow and limited cell division and remain in the resting zone until P21 indicating that the resting zone consists of more slowly dividing chondrocytes

• mice administered CREB inhibitor 666-15 from P7 to P27 exhibit partially restores bone growth and partially rescues abnormalities in structures of growth plate cartilage at P28, showing decreased heights of resting zone, increased proliferative and hypertrophic zones and increased height of the entire growth plate

abnormal long bone epiphyseal plate proliferative zone ( J:390604 )

• height of the proliferative zone is slightly reduced at P18 and is decreased at P21, P24, and P28

• the number of chondrocytes in proliferative zone is decreased, while the number of proliferating chondrocytes in the resting zones is similarly low as in controls

decreased width of hypertrophic chondrocyte zone ( J:390604 )

• the hypertrophic zone height is decreased at P21, P24, and P28

decreased long bone epiphyseal plate size ( J:390604 )

• the height of the growth plate cartilage is reduced at P21, P24, and P28

decreased length of long bones ( J:390604 )

• skeletal elements, including the femur, tibia, and ulna are shorter at P21

• degree of skeletal phenotypes appears more severe than that of patients with achondroplasia

short ulna ( J:390604 )

short femur ( J:390604 )

short tibia ( J:390604 )

abnormal chondrocyte differentiation ( J:390604 )

• the hypertrophic zone height is decreased at P21, P24, and P28, suggesting inhibition of terminal hypertrophic differentiation

delayed endochondral bone ossification ( J:390604 )

• formation of the secondary ossification center is slightly delayed at P16 but is clearly formed at P18

craniofacial

misaligned incisors ( J:390604 )

• incisors do not align normally because of changes in the skull

limbs/digits/tail

short ulna ( J:390604 )

short femur ( J:390604 )

short tibia ( J:390604 )

cellular

decreased chondrocyte proliferation ( J:390604 )

• the proliferative zone height is decreased at P21, P24, and P28, suggesting inhibition of chondrocyte proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
achondroplasia		DOID:4480	OMIM:100800	J:390604

Genotype
MGI:8404486

cn2

• Allelic Composition: Fgfr3^em1.1Ntsu/Fgfr3⁺; Gt(ROSA)26Sor^{tm1(CAG-Brainbow2.1)Cle}/Gt(ROSA)26Sor⁺; Tg(Col11a2-cre/ERT)#Ntsu/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6JJcl * C57BL/6NSlc

skeleton

abnormal long bone epiphyseal plate morphology ( J:390604 )

• mice administered tamoxifen at P20 show more variable angles of chondrocyte clonal cell stacks relative to the longitudinal axis of the growth plate cartilage suggesting that clonal progeny cells move in random directions and remain within the resting zone and do not move into the proliferative zone