Phenotypes associated with this allele

• Allele Symbol: Fgfr2^tm1Ewj
• Allele Name: targeted mutation 1, Ethylin Wang Jabs
• Allele ID: MGI:3603464
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Fgfr2^tm1Ewj/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	B6.Cg-Fgfr2^tm1Ewj Tg(EIIa-cre)C5379Lmgd	MGI:4440857
cn2	Fgfr2^tm1Ewj/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:3604025

Genotype
MGI:4440857

cn1

• Allelic Composition: Fgfr2^tm1Ewj/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: B6.Cg-Fgfr2^tm1Ewj Tg(EIIa-cre)C5379Lmgd

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

Skull analysis of Fgfr2^tm2Ewj/Fgfr2⁺ Tg(EIIa-cre)C5379Lmgd/0 and Fgfr2^tm1Ewj/Fgfr2⁺ Tg(EIIa-cre)C5379Lmgd/0 mice

skeleton

enhanced osteoblast differentiation ( J:158773 )

• as determined by marker expression, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

increased osteoblast proliferation ( J:158773 )

• osteoblast proliferation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

abnormal cranial suture morphology ( J:158773 )

• the suture between the horizontal plate of the palatine bone and palatal process of the maxilla is fused unlike in wild-type mice

abnormal coronal suture morphology ( J:158773 )

• coronal sutures exhibit increased osteogenic differentiation and accelerated bone growth compared to in wild-type mice

• however, apoptosis rates at coronal sutures is normal

abnormal intermaxillary suture morphology ( J:158773 )

• the inter-premaxillary suture appears patent unlike in wild-type mice

abnormal maxillary-premaxillary suture morphology ( J:158773 )

• mice exhibit premature closure of the premaxillary-maxillary sutures unlike wild-type mice

increased cranium height ( J:158773 )

• skull height is increased compared to in wild-type mice

small cranium ( J:158773 )

short mandible ( J:158773 )

short maxilla ( J:158773 )

• mice exhibit shorter maxilla than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice

premature coronal suture closure ( J:158773 )

• at P0, mice exhibit coronal suture presynostosis or synostosis unlike wild-type mice

premature zygomaticomaxillary suture closure ( J:158773 )

• mice exhibit premature closure of the suture between the zygomatic process of the maxilla and the zygomatic bones unlike wild-type mice

craniofacial

abnormal cranial suture morphology ( J:158773 )

• the suture between the horizontal plate of the palatine bone and palatal process of the maxilla is fused unlike in wild-type mice

abnormal coronal suture morphology ( J:158773 )

• coronal sutures exhibit increased osteogenic differentiation and accelerated bone growth compared to in wild-type mice

• however, apoptosis rates at coronal sutures is normal

abnormal intermaxillary suture morphology ( J:158773 )

• the inter-premaxillary suture appears patent unlike in wild-type mice

abnormal maxillary-premaxillary suture morphology ( J:158773 )

• mice exhibit premature closure of the premaxillary-maxillary sutures unlike wild-type mice

increased cranium height ( J:158773 )

• skull height is increased compared to in wild-type mice

small cranium ( J:158773 )

short mandible ( J:158773 )

short maxilla ( J:158773 )

• mice exhibit shorter maxilla than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice

abnormal palate morphology ( J:158773 )

• the most posterior portion of the palate is reduced compared to in wild-type mice

abnormal palatal shelf fusion at midline ( J:158773 )

• the midline suture between the horizontal plates of the palatine bones is patent compared to controls

• in 1 of 8 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 7 of 12 wild-type mice

decreased palatal length ( J:158773 )

• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

digestive/alimentary system

abnormal palate morphology ( J:158773 )

• the most posterior portion of the palate is reduced compared to in wild-type mice

abnormal palatal shelf fusion at midline ( J:158773 )

• the midline suture between the horizontal plates of the palatine bones is patent compared to controls

• in 1 of 8 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 7 of 12 wild-type mice

decreased palatal length ( J:158773 )

• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

cellular

enhanced osteoblast differentiation ( J:158773 )

• as determined by marker expression, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

increased osteoblast proliferation ( J:158773 )

• osteoblast proliferation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

vision/eye

decreased inner canthal distance ( J:158773 )

• intercanthal distance is reduced compared to in wild-type mice

growth/size/body

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice

abnormal palate morphology ( J:158773 )

• the most posterior portion of the palate is reduced compared to in wild-type mice

abnormal palatal shelf fusion at midline ( J:158773 )

• the midline suture between the horizontal plates of the palatine bones is patent compared to controls

• in 1 of 8 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 7 of 12 wild-type mice

decreased palatal length ( J:158773 )

• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2^tm2Ewj heterozygotes

respiratory system

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice

Genotype
MGI:3604025

cn2

• Allelic Composition: Fgfr2^tm1Ewj/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:101174 )

• mutants with complete recombination die within 24 -36 hours of birth; however, 2 mutants with only partial recombination survived to adulthood

respiratory system

abnormal nasal bone morphology ( J:101174 )

• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age

pulmonary alveolar proteinosis ( J:101174 )

• presence of proteinaceous fluid in the alveoli is observed

bronchiolectasis ( J:101174 )

• multifocal and acute bronchiolectasis with mild dilation of the bronchioles are seen in mutants with complete recombination

atelectasis ( J:101174 )

• moderate and diffuse atelectasis with lack of alveolar expansion and the presence of proteinaceous fluid in the alveoli is observed

abnormal tracheal cartilage morphology ( J:101174 )

• a complete cartilage sleeve surrounds the trachea in mutants with complete recombination

respiratory failure ( J:101174 )

• seen in mutants with complete recombination

skeleton

abnormal osteoblast differentiation ( J:101174 )

• at E18.5 in mutants with complete recombination, markers of osteoblast differentiation are seen in cells from the edge of the bone plates into the mid-sutural area of the saggital suture where preosteoblasts are not normally found

• at E18.5 in mutants with complete recombination no differentiating osteoblasts are found between the osteogenic fronts unlike in wild-type mice

abnormal craniofacial bone morphology ( J:101174 )

abnormal cranial suture morphology ( J:101174 )

• in mutants with only partial recombination at 10 months of age multiple interfrontal suture defects are seen and the fronto-premaxillary, premaxillary-maxillary, and nasal-frontal sutures are obliterated

wide metopic suture ( J:101174 )

• at P1 in mutants with complete recombination the space between the osteogenic fronts is increased

• at E18.5 in mutants with complete recombination increased numbers of proliferating cells are seen between the osteogenic fronts and no differentiating osteoblasts are found between the osteogenic fronts unlike in wild-type mice

abnormal sagittal suture morphology ( J:101174 )

• at E16.5 and E18.5 in mutants with complete recombination ectopic cartilage is found along all (E16.5) or over half (E18.5) of the length of the suture

• at E18.5 in mutants with complete recombination the space between the osteogenic fronts is decreased and at P1 the osteogenic fronts are very close and osteoid is deposited between the fronts prior to synostosis

• at E18.5 and P1 in mutants with complete recombination twice as many proliferating cells are seen and some of these cells are abnormally distributed in the space between the osteogenic fronts

• at E18.5 in mutants with complete recombination, markers of osteoblast differentiation are seen in cells from the edge of the bone plates into the mid-sutural area of the saggital suture where preosteoblasts are not normally found

abnormal basicranium morphology ( J:101174 )

• increased cartilage is found on the basicranium at birth in mutants with complete recombination

• structures of the basicranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age

decreased cranium height ( J:101174 )

• skull height is significantly reduced in mutants with complete recombination

decreased cranium length ( J:101174 )

• skull length is significantly reduced in mutants with complete recombination

small cranium ( J:101174 )

• skull length and height are significantly reduced in mutants with complete recombination

• in mutants with only partial recombination at 10 months of age skull width is more affected than skull length resulting in a brachycephalic skull shape

abnormal interparietal bone morphology ( J:101174 )

• the interparietal bone is compressed superiorly at the lambdoid suture in mutants with only partial recombination at 10 months of age

parietal bossing ( J:101174 )

• the parietal bones have an obvious superior bulge in mutants with only partial recombination at 10 months of age

abnormal zygomatic arch morphology ( J:101174 )

• the temporal process of the zygomatic bone is fused to the zygomatic process of the temporal bone in mutants with complete recombination

small neurocranium ( J:101174 )

• structures of the neurocranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age

abnormal mandible morphology ( J:101174 )

abnormal mandibular angle morphology ( J:101174 )

• dysmorphic angular process in mutants with only partial recombination at 10 months of age

small mandible ( J:101174 )

• the mandible is very small in mutants with only partial recombination at 10 months of age

abnormal maxillary frontal process morphology ( J:101174 )

• the frontal process of the maxilla has an abnormally large sinus and bowing of the medial wall in mutants with only partial recombination at 10 months of age

abnormal maxillary zygomatic process morphology ( J:101174 )

• the zygomatic process is bowed more laterally in mutants with only partial recombination at 10 months of age

short maxilla ( J:101174 )

• seen in mutants with complete recombination

abnormal nasal bone morphology ( J:101174 )

• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age

decreased osteoclast cell number ( J:101174 )

• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones

abnormal cartilage morphology ( J:101174 )

• the nasal cartilage is thickened

abnormal tracheal cartilage morphology ( J:101174 )

• a complete cartilage sleeve surrounds the trachea in mutants with complete recombination

abnormal cartilage development ( J:101174 )

• in mutants with complete recombination, more prominent cartilage mineralization is seen in the long bones at P1; however, limb lengths are proportional to body size and no syndactyly is seen

abnormal long bone hypertrophic chondrocyte zone ( J:101174 )

• in mutants with complete recombination, the hypertrophic zone of the growth plate of the long bones is subtly irregular

premature cranial suture closure ( J:101174 )

• seen in 6 of 9 mutants with complete recombination

premature coronal suture closure ( J:101174 , J:156940 )

• at P1 in mutants with complete recombination synostosis with osteoid deposition is seen (J:101174)

• at P0, mice exhibit variation in the pattern and degree of coronal suture closure compared with wild-type mice (J:156940)

• mice exhibit unilateral or bilateral coronal suture synostosis unlike wild-type mice (J:156940)

premature lambdoid suture closure ( J:101174 )

• at P1 in mutants with complete recombination synostosis with osteoid deposition is seen

growth/size/body

abnormal nasal bone morphology ( J:101174 )

• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age

small face ( J:101174 )

• structures of the face are about 40-50% smaller in mutants with only partial recombination at 10 months of age

abnormal palate morphology ( J:101174 )

• malformations of the palate are seen in all mutants

abnormal head shape ( J:101174 )

• in mutants with only partial recombination at 10 months of age head shape is abnormal

shortened head ( J:101174 )

• in mutants with only partial recombination at 10 months of age skull width is more affected than skull length resulting in a brachycephalic skull shape

meteorism ( J:101174 )

• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination

decreased birth weight ( J:101174 )

• at birth in mutants with complete recombination body weight is about 83% that of wild-type littermates

decreased body weight ( J:101174 )

• in mutants with only partial recombination at 10 months of age body weight is 29% that of wild-type littermates

decreased body length ( J:101174 )

• in mutants with only partial recombination at 10 months of age body length is 68% that of wild-type littermates

cardiovascular system

dilated heart atrium ( J:101174 )

• mild dilation of the atria is seen in mutants with complete recombination

abnormal vasodilation ( J:101174 )

• mild dilation of the great vessels at the base of the heart is seen in mutants with complete recombination

immune system

abnormal thymus morphology ( J:101174 )

• diffuse lymphoid necrosis and apoptosis of variable severity is seen in mutants with complete recombination

decreased osteoclast cell number ( J:101174 )

• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones

bronchiolectasis ( J:101174 )

• multifocal and acute bronchiolectasis with mild dilation of the bronchioles are seen in mutants with complete recombination

nervous system

abnormal brain morphology ( J:156940 )

• 4 of 10 mice exhibit severe brain asymmetry unlike in wild-type mice

• 1 of 10 mice exhibit mild brain asymmetry unlike in wild-type mice

• rostrocaudal brain length is decreased compared to in wild-type mice

hydrocephaly ( J:101174 )

• mild hydroencephaly with enlarged ventricles is present in mutants with complete recombination

increased brain size ( J:156940 )

enlarged fourth ventricle ( J:156940 )

• in 2 of 10 mice

abnormal cerebral hemisphere morphology ( J:156940 )

• cerebral height is increased compared to in wild-type mice

• mice exhibit cerebral asymmetry to varying degrees compared with wild-type mice

abnormal corpus callosum morphology ( J:156940 )

• arched in 2 of 10 mice

craniofacial

abnormal craniofacial bone morphology ( J:101174 )

abnormal cranial suture morphology ( J:101174 )

• in mutants with only partial recombination at 10 months of age multiple interfrontal suture defects are seen and the fronto-premaxillary, premaxillary-maxillary, and nasal-frontal sutures are obliterated

wide metopic suture ( J:101174 )

• at P1 in mutants with complete recombination the space between the osteogenic fronts is increased

• at E18.5 in mutants with complete recombination increased numbers of proliferating cells are seen between the osteogenic fronts and no differentiating osteoblasts are found between the osteogenic fronts unlike in wild-type mice

abnormal sagittal suture morphology ( J:101174 )

• at E16.5 and E18.5 in mutants with complete recombination ectopic cartilage is found along all (E16.5) or over half (E18.5) of the length of the suture

• at E18.5 in mutants with complete recombination the space between the osteogenic fronts is decreased and at P1 the osteogenic fronts are very close and osteoid is deposited between the fronts prior to synostosis

• at E18.5 and P1 in mutants with complete recombination twice as many proliferating cells are seen and some of these cells are abnormally distributed in the space between the osteogenic fronts

• at E18.5 in mutants with complete recombination, markers of osteoblast differentiation are seen in cells from the edge of the bone plates into the mid-sutural area of the saggital suture where preosteoblasts are not normally found

abnormal basicranium morphology ( J:101174 )

• increased cartilage is found on the basicranium at birth in mutants with complete recombination

• structures of the basicranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age

decreased cranium height ( J:101174 )

• skull height is significantly reduced in mutants with complete recombination

decreased cranium length ( J:101174 )

• skull length is significantly reduced in mutants with complete recombination

small cranium ( J:101174 )

• skull length and height are significantly reduced in mutants with complete recombination

• in mutants with only partial recombination at 10 months of age skull width is more affected than skull length resulting in a brachycephalic skull shape

abnormal interparietal bone morphology ( J:101174 )

• the interparietal bone is compressed superiorly at the lambdoid suture in mutants with only partial recombination at 10 months of age

parietal bossing ( J:101174 )

• the parietal bones have an obvious superior bulge in mutants with only partial recombination at 10 months of age

abnormal zygomatic arch morphology ( J:101174 )

• the temporal process of the zygomatic bone is fused to the zygomatic process of the temporal bone in mutants with complete recombination

small neurocranium ( J:101174 )

• structures of the neurocranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age

abnormal mandible morphology ( J:101174 )

abnormal mandibular angle morphology ( J:101174 )

• dysmorphic angular process in mutants with only partial recombination at 10 months of age

small mandible ( J:101174 )

• the mandible is very small in mutants with only partial recombination at 10 months of age

abnormal maxillary frontal process morphology ( J:101174 )

• the frontal process of the maxilla has an abnormally large sinus and bowing of the medial wall in mutants with only partial recombination at 10 months of age

abnormal maxillary zygomatic process morphology ( J:101174 )

• the zygomatic process is bowed more laterally in mutants with only partial recombination at 10 months of age

short maxilla ( J:101174 )

• seen in mutants with complete recombination

abnormal nasal bone morphology ( J:101174 )

• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age

small face ( J:101174 )

• structures of the face are about 40-50% smaller in mutants with only partial recombination at 10 months of age

abnormal palate morphology ( J:101174 )

• malformations of the palate are seen in all mutants

abnormal head shape ( J:101174 )

• in mutants with only partial recombination at 10 months of age head shape is abnormal

shortened head ( J:101174 )

• in mutants with only partial recombination at 10 months of age skull width is more affected than skull length resulting in a brachycephalic skull shape

hematopoietic system

abnormal thymus morphology ( J:101174 )

• diffuse lymphoid necrosis and apoptosis of variable severity is seen in mutants with complete recombination

decreased osteoclast cell number ( J:101174 )

• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones

digestive/alimentary system

abnormal palate morphology ( J:101174 )

• malformations of the palate are seen in all mutants

aerophagia ( J:101174 )

• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination

meteorism ( J:101174 )

• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination

muscle

abnormal vasodilation ( J:101174 )

• mild dilation of the great vessels at the base of the heart is seen in mutants with complete recombination

homeostasis/metabolism

pulmonary alveolar proteinosis ( J:101174 )

• presence of proteinaceous fluid in the alveoli is observed

cellular

abnormal osteoblast differentiation ( J:101174 )

• at E18.5 in mutants with complete recombination, markers of osteoblast differentiation are seen in cells from the edge of the bone plates into the mid-sutural area of the saggital suture where preosteoblasts are not normally found

• at E18.5 in mutants with complete recombination no differentiating osteoblasts are found between the osteogenic fronts unlike in wild-type mice

endocrine/exocrine glands

abnormal thymus morphology ( J:101174 )

• diffuse lymphoid necrosis and apoptosis of variable severity is seen in mutants with complete recombination

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:101174 , J:156940