Phenotypes associated with this allele

• Allele Symbol: Fgfr2⁺
• Allele Name: wild type
• Allele ID: MGI:2156175
• Summary: 27 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Fgfr2^tm3Ewj/Fgfr2^+	B6.129-Fgfr2^tm3Ewj	MGI:5450965
ht2	Fgfr2^tm1Cxd/Fgfr2^+	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * NIH Black Swiss)	MGI:2176478
ht3	Fgfr2^tm2.2Dsn/Fgfr2^+	involves: 129 * C57BL/6 * FVB/N	MGI:2176482
ht4	Fgfr2^tm2.3Dsn/Fgfr2^+	involves: 129 * C57BL/6 * FVB/N	MGI:2176483
ht5	Fgfr2^tm1.1Dsn/Fgfr2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:2173369
ht6	Fgfr2^tm1Schl/Fgfr2^+	involves: 129S1/Sv	MGI:3699817
ht7	Fgfr2^tm2Ewj/Fgfr2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:4430189
ht8	Fgfr2^tm2Schl/Fgfr2^+	involves: 129S1/Sv * BALB/c * C57BL/6	MGI:3699820
ht9	Fgfr2^tm3.1Cxd/Fgfr2^+	involves: 129S6/SvEvTac * FVB/N	MGI:6407058
ht10	Fgfr2^m1Sgg/Fgfr2^+	involves: C3H/HeJ * C57BL/6J	MGI:4461807
ht11	Fgfr2^tm4Lni/Fgfr2^+	Not Specified	MGI:3053579
cn12	Fgfr2^tm1Ewj/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	B6.Cg-Fgfr2^tm1Ewj Tg(EIIa-cre)C5379Lmgd	MGI:4440857
cn13	Fgfr2^tm2Ewj/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	B6.Cg-Fgfr2^tm2Ewj Tg(EIIa-cre)C5379Lmgd	MGI:4440856
cn14	Fgfr2^tm1Dor/Fgfr2^+ Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd Foxg1^tm1(cre)Skm/Foxg1^+ Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Frs3^tm1Jheb/Frs3^tm1Jheb	involves: 129	MGI:6116892
cn15	Fgfr2^tm2Dsn/Fgfr2^+ Tg(Pgk1-cre)1Lni/0	involves: 129 * 129X1/SvJ * BALB/c * C57BL/6	MGI:3775811
cn16	Fgf10^tm1Wss/Fgf10^+ Fgfr2^tm2Dsn/Fgfr2^+ Tg(Pgk1-cre)1Lni/0	involves: 129 * 129X1/SvJ * BALB/c * C57BL/6	MGI:3775807
cn17	Fgfr1^tm1Jpa/Fgfr1^tm1.1Jpa Fgfr2^tm1Dor/Fgfr2^+ Twist2^tm1(cre)Dor/Twist2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3813483
cn18	Fgfr2^tm1Ewj/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:3604025
cn19	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^+ Tg(Pax3-cre)1Joe/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5438670
cn20	Fgfr2^tm3Cxd/Fgfr2^+ Tg(Nes-cre)1Kln/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL	MGI:6415681
cn21	Fgfr2^tm3Cxd/Fgfr2^+ Tg(Col2a1-cre)1Xya/0	involves: 129S6/SvEvTac * C57BL/6J	MGI:6415627
cn22	Fgfr2^tm2Cxd/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:5790180
cn23	Fgfr2^tm2Cxd/Fgfr2^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S6/SvEvTac * FVB/N	MGI:3604078
cn24	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^+ Tg(Hoxb7-cre)5526Cmb/0	involves: FVB/N	MGI:3525679
cx25	Fgfr2^tm1.1Dor/Fgfr2^+ Spry2^tm1.1Mrt/Spry2^tm1.1Mrt	involves: 129P2/OlaHsd * 129X1/SvJ	MGI:3702560
cx26	Fgfr2^tm3.1Lni/Fgfr2^+ Hmgcs2^em1Wilh/Hmgcs2^em1Wilh	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6416132
cx27	Fgfr2^tm1.1Dor/Oat^rhg	involves: AKR/J * C57BL/6J * C57BL/6JEi * FVB/N	MGI:6162253

Genotype
MGI:5450965

ht1

• Allelic Composition: Fgfr2^tm3Ewj/Fgfr2⁺
• Genetic Background: B6.129-Fgfr2^tm3Ewj

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

Fgfr2^tm3Ewj/Fgfr2⁺ mice have cutis gyrata, acanthosis, skull synostosis, and other abnormalities

mortality/aging

postnatal lethality, complete penetrance ( J:190491 )

• almost half of the mutants die within 24-36 hours after birth and most die within 2 weeks of age

growth/size/body

midface hypoplasia ( J:190491 )

• midfacial hypoplasia

• treatment with SB203580, a p38 kinase inhibitor, reduces epidermal and skull abnormalities but does not improve the survival of mutants, however, treatment with MEK/ERK inhibitor U0126 has no effect

abnormal head shape ( J:190491 )

• P0 heterozygotes exhibit dome-shaped heads

shortened head ( J:190491 )

• brachycephalic-shaped skull

postnatal growth retardation ( J:190491 )

• mutants exhibit reduced growth with age

craniofacial

midface hypoplasia ( J:190491 )

• midfacial hypoplasia

• treatment with SB203580, a p38 kinase inhibitor, reduces epidermal and skull abnormalities but does not improve the survival of mutants, however, treatment with MEK/ERK inhibitor U0126 has no effect

abnormal head shape ( J:190491 )

• P0 heterozygotes exhibit dome-shaped heads

shortened head ( J:190491 )

• brachycephalic-shaped skull

embryo

abnormal umbilical cord morphology ( J:190491 )

• protruding and enlarged umbilical stump

integument

abnormal skin morphology ( J:190491 )

• skin of E16.5, P0 and P5 mutants shows typical furrowing and thickening similar to cutis gyrata and acanthosis, and papillomatosis

• treatment with SB203580, a p38 kinase inhibitor, reduces epidermal and skull abnormalities but does not improve the survival of mutants, however, treatment with MEK/ERK inhibitor U0126 has no effect

abnormal dermis papillary layer morphology ( J:190491 )

• skin at E16.5, P0 and P5 shows papillomatosis and height measurements of the top and bottom of the troughs of the papillomatosis are higher in mutants than in wild-type mice

abnormal epidermis stratum basale morphology ( J:190491 )

• basal layer of the epidermis shows an increase in cell proliferation

abnormal epidermis stratum corneum morphology ( J:190491 )

• hyperplastic cells in the cornified layer

epidermis stratum granulosum hyperplasia ( J:190491 )

epidermis stratum spinosum hyperplasia ( J:190491 )

acanthosis ( J:190491 )

epidermal hyperplasia ( J:190491 )

thick epidermis ( J:190491 )

• at E16.5, P0 and P5

skeleton

abnormal sternum morphology ( J:190491 )

• fusion of bones of the sternum

premature cranial suture closure ( J:190491 )

• premature fusion of the coronal and squamosal sutures

premature coronal suture closure ( J:190491 )

• marker analysis indicates an increase in osteogenic differentiation and abnormal bone growth at the coronal suture

• the coronal suture exhibits synostosis and presynostosis at E17.5, showing deposition of osteoid between the osteogenic fronts

premature squamoparietal suture closure ( J:190491 )

• premature fusion of the squamosal sutures

premature zygomaticomaxillary suture closure ( J:190491 )

• premature fusion of the zygomaxillary sutures

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Beare-Stevenson cutis gyrata syndrome		DOID:0050660	OMIM:123790	J:190491

Genotype
MGI:2176478

ht2

• Allelic Composition: Fgfr2^tm1Cxd/Fgfr2⁺
• Genetic Background: either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * NIH Black Swiss)

normal phenotype

no abnormal phenotype detected ( J:46380 )

• surprisingly, heterozygotes are developmentally normal with no craniofacial or limb defects

Genotype
MGI:2176482

ht3

• Allelic Composition: Fgfr2^tm2.2Dsn/Fgfr2⁺
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

normal phenotype

no abnormal phenotype detected ( J:72517 )

Genotype
MGI:2176483

ht4

• Allelic Composition: Fgfr2^tm2.3Dsn/Fgfr2⁺
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

Percocious ossification of coronal sutures and the sternum in Fgfr2^tm2.3Dsn/Fgfr2⁺ mice

mortality/aging

postnatal lethality, complete penetrance ( J:72517 )

• mice died within 9 days of birth

craniofacial

abnormal neurocranium morphology ( J:72517 )

• rounded skull with dorso ventral extension of the cranium

abnormal zygomatic arch morphology ( J:72517 )

• zygomatic arch bones were fused at their joints

shallow orbits ( J:72517 )

short maxilla ( J:72517 )

• associated with the premature coronal suture fusion

domed cranium ( J:72517 )

short snout ( J:72517 )

digestive/alimentary system

digestive/alimentary phenotype ( J:72517 )

N • normal stomach and gut architecture and innervation

abnormal intestinal glucose absorption ( J:72517 )

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:72517 )

N • adrenal glands were of normal size

absent exorbital lacrimal gland ( J:72517 )

• P1 mutants show a lack of exorbital lacrimal gland development

growth/size/body

short snout ( J:72517 )

decreased body size ( J:72517 )

• 90% are slightly smaller at birth

postnatal growth retardation ( J:72517 )

• mutants do not gain weight after birth and die within 9 days

homeostasis/metabolism

hypoglycemia ( J:72517 )

• putatively due to malnutrition resulting from a gastrointestinal defect

liver/biliary system

abnormal liver development ( J:72517 )

• mild lobulation defect

renal/urinary system

abnormal kidney cortex morphology ( J:72517 )

• fewer glomeruli relative to wild-type

decreased renal glomerulus number ( J:72517 )

• fewer and degenerating glomeruli are seen at P2

small kidney ( J:72517 )

• kidneys did not grow beyond their birth size

decreased nephron number ( J:72517 )

• fewer developing nephrons in the cortical region at E14.5

dilated distal convoluted tubule ( J:72517 )

• distal tubules are dilated

dilated proximal convoluted tubule ( J:72517 )

• proximal tubules are dilated

respiratory system

abnormal lung morphology ( J:72517 )

• lung mesenchyme is more compact and often congested with red blood cells at P1

impaired lung alveolus development ( J:72517 )

• incomplete aveolarization

impaired lung lobe morphogenesis ( J:72517 )

• partial lobulation of the right lung

small lung ( J:72517 )

abnormal pulmonary acinus morphology ( J:72517 )

• fewer bronchioles lined with ciliated cells and fewer branched alveolar structures

abnormal bronchiole morphology ( J:72517 )

• development of fewer bronchioles lined with ciliated cells

abnormal right lung morphology ( J:72517 )

• three partially separated pulmonary lobes rather than the four observed in wild-type

skeleton

abnormal neurocranium morphology ( J:72517 )

• rounded skull with dorso ventral extension of the cranium

abnormal zygomatic arch morphology ( J:72517 )

• zygomatic arch bones were fused at their joints

shallow orbits ( J:72517 )

short maxilla ( J:72517 )

• associated with the premature coronal suture fusion

domed cranium ( J:72517 )

abnormal sternebra morphology ( J:72517 )

• individual sternebrae are thicker and less congruent

split sternal manubrium ( J:72517 )

• manubrium is bifurcated

split xiphoid process ( J:72517 )

abnormal sternum ossification ( J:72517 )

• abnormal ossification of the intersternebral cartilage, first observed at E16.5

premature coronal suture closure ( J:72517 )

• ossification of the coronal sutures by E18

vision/eye

shallow orbits ( J:72517 )

absent exorbital lacrimal gland ( J:72517 )

• P1 mutants show a lack of exorbital lacrimal gland development

exophthalmos ( J:72517 )

• due to shallow orbits resulting from zygomatic bone abnormalities

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:72517
Pfeiffer syndrome		DOID:14705	OMIM:101600	J:72517

Genotype
MGI:2173369

ht5

• Allelic Composition: Fgfr2^tm1.1Dsn/Fgfr2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

Hypoplastic submandibular glands are seen in Fgfr2^tm1.1Dsn/Fgfr2⁺ and Fgf10^tm1Ska/Fgf10⁺ mice

endocrine/exocrine glands

abnormal submandibular duct morphology ( J:119849 )

• at E13.5, glands have fewer ducts and terminal buds

submandibular gland hypoplasia ( J:119849 )

• submandibular salivary gland branching hypoplasia at E13.5

digestive/alimentary system

abnormal submandibular duct morphology ( J:119849 )

• at E13.5, glands have fewer ducts and terminal buds

submandibular gland hypoplasia ( J:119849 )

• submandibular salivary gland branching hypoplasia at E13.5

Genotype
MGI:3699817

ht6

• Allelic Composition: Fgfr2^tm1Schl/Fgfr2⁺
• Genetic Background: involves: 129S1/Sv

Crouzon-Like Syndrome characterization, skull scan and histological sections of Fgfr2^tm1Schl/Fgfr2⁺ and Fgfr2^tm2Schl/Fgfr2⁺ mice

craniofacial

abnormal cranium morphology ( J:118299 )

• mice have rounded cranium

short face ( J:118299 )

• facial region is significantly shortened

growth/size/body

short face ( J:118299 )

• facial region is significantly shortened

skeleton

abnormal cranium morphology ( J:118299 )

• mice have rounded cranium

premature cranial suture closure ( J:118299 )

• mice display craniosynostosis

premature coronal suture closure ( J:118299 )

• at 6 weeks of age, coronal sutures are fused completely on both sides of the skull, unlike in wild-type controls

• 1-week old mice have abundant mineralized bone trabeculae in the coronal suture mesenchyme

vision/eye

exophthalmos ( J:118299 )

• mice have protruding eyes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Crouzon syndrome		DOID:2339	OMIM:123500	J:118299

Genotype
MGI:4430189

ht7

• Allelic Composition: Fgfr2^tm2Ewj/Fgfr2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

abnormal brain morphology ( J:156940 )

• 1 of 14 mice exhibit severe brain asymmetry unlike in wild-type mice

• 1 of 14 mice exhibit mild brain asymmetry unlike in wild-type mice

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

enlarged fourth ventricle ( J:156940 )

• in 2 of 14 mice

enlarged lateral ventricles ( J:156940 )

• in 1 of 14 mice

abnormal cerebral hemisphere morphology ( J:156940 )

• cerebral height in many mice 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 3 of 14 mice

skeleton

premature coronal suture closure ( J:156940 )

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

• mice exhibit unilateral or bilateral coronal suture synostosis unlike wild-type mice

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

Genotype
MGI:3699820

ht8

• Allelic Composition: Fgfr2^tm2Schl/Fgfr2⁺
• Genetic Background: involves: 129S1/Sv * BALB/c * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:118299 )

• mice are normal and indistinguishable from wild-type, with no craniofacial phenotype like Fgfr2^tm2Schl heterozygotes

Genotype
MGI:6407058

ht9

• Allelic Composition: Fgfr2^tm3.1Cxd/Fgfr2⁺
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

mortality/aging

premature death ( J:283626 )

• 45% of mice die within 6 months and the remaining 20% survive to adulthood

postnatal lethality, incomplete penetrance ( J:283626 )

• about 35% of mice die before P20

growth/size/body

malocclusion ( J:283626 )

abnormal midface morphology ( J:283626 )

• underdeveloped midface accompanied by malocclusion

midface hypoplasia ( J:283626 )

shortened head ( J:283626 )

decreased body size ( J:283626 )

decreased body weight ( J:283626 )

• weight at birth is 90% of wild-type and by 3 weeks of age, mice are 40-50% smaller than controls

postnatal growth retardation ( J:283626 )

• severe growth retardation

craniofacial

abnormal craniofacial morphology ( J:283626 )

• mutants exhibit mild craniofacial malformation beginning from E16.5 and show more obvious head malformation with age

abnormal cranium morphology ( J:283626 )

• some mice show a distorted skull

• the distance between nasale and nasion is the most severely affected distance

• increase in skull breadth

short basicranium ( J:283626 )

abnormal cranial cartilage development ( J:283626 )

• mutants show cartilages in the sagittal sutures at P2, indicating abnormal cartilage formation at the sagittal sutures

• cartilage is not present in the posterior frontal sutures at P8 and the sutures remain patent at P17

abnormal cranial synchondrosis ( J:283626 )

• mice show growth retardation of the synchondroses of cranial base

decreased cranium length ( J:283626 )

increased cranium height ( J:283626 )

increased cranium width ( J:283626 )

• the cranial width is increased between paired frontal bones and less increased between paired parietal bones

malocclusion ( J:283626 )

domed cranium ( J:283626 )

• dome-shaped skulls are seen beginning at E16.5

abnormal midface morphology ( J:283626 )

• underdeveloped midface accompanied by malocclusion

midface hypoplasia ( J:283626 )

shortened head ( J:283626 )

cellular

enhanced osteoblast differentiation ( J:283626 )

• marker analysis suggests enhanced osteoblast differentiation in the cranium

skeleton

enhanced osteoblast differentiation ( J:283626 )

• marker analysis suggests enhanced osteoblast differentiation in the cranium

abnormal cranium morphology ( J:283626 )

• some mice show a distorted skull

• the distance between nasale and nasion is the most severely affected distance

• increase in skull breadth

short basicranium ( J:283626 )

abnormal cranial cartilage development ( J:283626 )

• mutants show cartilages in the sagittal sutures at P2, indicating abnormal cartilage formation at the sagittal sutures

• cartilage is not present in the posterior frontal sutures at P8 and the sutures remain patent at P17

abnormal cranial synchondrosis ( J:283626 )

• mice show growth retardation of the synchondroses of cranial base

decreased cranium length ( J:283626 )

increased cranium height ( J:283626 )

increased cranium width ( J:283626 )

• the cranial width is increased between paired frontal bones and less increased between paired parietal bones

malocclusion ( J:283626 )

domed cranium ( J:283626 )

• dome-shaped skulls are seen beginning at E16.5

abnormal long bone epiphyseal ossification zone morphology ( J:283626 )

• appearance of the first and second ossification centers is delayed in tibial epiphysis

abnormal long bone epiphyseal plate proliferative zone ( J:283626 )

• long bones show shortened zones of proliferating chondrocytes

• number of proliferating chondrocytes in growth plates of the proximal tibia is decreased

decreased width of hypertrophic chondrocyte zone ( J:283626 )

• long bones show shortened zones of hypertrophic chondrocytes

abnormal long bone epiphysis morphology ( J:283626 )

• long bones show decreased trabecular bone areas in the growth plates

abnormal trabecular bone morphology ( J:283626 )

• long bones show decreased trabecular bone areas in the growth plates

abnormal synchondrosis ( J:283626 )

• mice show growth retardation of the synchondroses of growth plates of long bones

• retarded growth of synchondroses is seen at the late embryonic period and results in shortening of the cranial base

abnormal endochondral bone ossification ( J:283626 )

• endochondral ossification is retarded, with mice showing shortened synchondroses of cranial base in late embryonic and neonatal stages and delayed appearance of ossification centers in tibia and retarded long bone growth

• treatment of cultured femur with PD98059, an ERK1/2 inhibitor, results in partially alleviated growth retardation of femur

delayed cranial suture closure ( J:283626 )

• mice show delayed fusion of posterior frontal sutures

• however, premature fusion of the intersphenoidal and sphenooccipital synchondroses is not seen

premature intramembranous bone ossification ( J:283626 )

• accelerated intramembranous ossification in the cranium, which is apparent at late embryonic stages

premature coronal suture closure ( J:283626 )

• mice have fewer mesenchymal cells between the osteogenic fronts of the frontal and parietal bones and coronal sutures close prematurely

• treatment of cultured calvaria and femur with PD98059, an ERK1/2 inhibitor, results in partially alleviated coronal suture fusion

embryo

short rostral-caudal axis ( J:283626 )

limbs/digits/tail

syndactyly ( J:283626 )

• 3 mice show syndactyly

vision/eye

ocular hypertelorism ( J:283626 )

respiratory system

respiratory system phenotype ( J:283626 )

N • no gross or histological abnormalities are seen in the lungs

cardiovascular system

cardiovascular system phenotype ( J:283626 )

N • no gross or histological abnormalities are seen in the heart

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:283626

Genotype
MGI:4461807

ht10

• Allelic Composition: Fgfr2^m1Sgg/Fgfr2⁺
• Genetic Background: involves: C3H/HeJ * C57BL/6J

craniofacial

abnormal craniofacial morphology ( J:160674 )

• at 3 weeks of age, mice exhibit short snout, retruded mid-face, and variable septal deviation unlike wild-type mice

wide cranial sutures ( J:160674 )

• sutural spaces are wider than in wild-type mice

abnormal basisphenoid bone morphology ( J:160674 )

decreased cranium height ( J:160674 )

• mice exhibit decreased antero-posterior skull length compared with wild-type mice

absent presphenoid bone ( J:160674 )

long incisors ( J:160674 )

malocclusion ( J:160674 )

domed cranium ( J:160674 )

abnormal palatal shelf fusion at midline ( J:160674 )

• mice exhibit a delay in horizontal secondary palate formation in the posterior edge of the maxillary bone and hard tissue clefts on the secondary palate compared with wild-type mice

cleft secondary palate ( J:160674 )

abnormal nasal septum cartilage morphology ( J:160674 )

• nasal septum shows a lack of ordered columnar organization of chondrocytes compared to in wild-type mice

short snout ( J:160674 )

growth/size/body

growth/size/body region phenotype ( J:160674 )

N • 3 weeks postnatal, mice exhibit normal body size and weight

long incisors ( J:160674 )

malocclusion ( J:160674 )

abnormal palatal shelf fusion at midline ( J:160674 )

• mice exhibit a delay in horizontal secondary palate formation in the posterior edge of the maxillary bone and hard tissue clefts on the secondary palate compared with wild-type mice

cleft secondary palate ( J:160674 )

abnormal nasal septum cartilage morphology ( J:160674 )

• nasal septum shows a lack of ordered columnar organization of chondrocytes compared to in wild-type mice

short snout ( J:160674 )

decreased embryo size ( J:160674 )

decreased birth body size ( J:160674 )

• slightly

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:160674 )

• mice exhibit a delay in horizontal secondary palate formation in the posterior edge of the maxillary bone and hard tissue clefts on the secondary palate compared with wild-type mice

cleft secondary palate ( J:160674 )

embryo

decreased embryo size ( J:160674 )

hearing/vestibular/ear

abnormal ear development ( J:160674 )

• the ear capsule is reduced in size compared to in wild-type mice

respiratory system

abnormal nasal septum cartilage morphology ( J:160674 )

• nasal septum shows a lack of ordered columnar organization of chondrocytes compared to in wild-type mice

skeleton

wide cranial sutures ( J:160674 )

• sutural spaces are wider than in wild-type mice

abnormal basisphenoid bone morphology ( J:160674 )

decreased cranium height ( J:160674 )

• mice exhibit decreased antero-posterior skull length compared with wild-type mice

absent presphenoid bone ( J:160674 )

long incisors ( J:160674 )

malocclusion ( J:160674 )

domed cranium ( J:160674 )

abnormal nasal septum cartilage morphology ( J:160674 )

• nasal septum shows a lack of ordered columnar organization of chondrocytes compared to in wild-type mice

abnormal sternum morphology ( J:160674 )

decreased osteoblast cell number ( J:160674 )

• fewer Runx2+ cells are found surrounding the edge of the coronal sutures compared to in wild-type mice

abnormal chondrocyte morphology ( J:160674 )

• pericellular spaces in the nasal septum chondrocytes are bigger than in wild-type mice

abnormal endochondral bone ossification ( J:160674 )

premature coronal suture closure ( J:160674 )

• premature fusion in some mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Crouzon syndrome		DOID:2339	OMIM:123500	J:160674

Genotype
MGI:3053579

ht11

• Allelic Composition: Fgfr2^tm4Lni/Fgfr2⁺
• Genetic Background: Not Specified

Skull and coronal suture phenotypes of Fgfr2^tm4Lni/ Fgfr2⁺ (Fgfr2c^C342Y/+) mice.

craniofacial

abnormal frontal bone morphology ( J:235329 )

• elastic modulus of the frontal bone is lower than in wild-type mice at P10 and P20 and is lower than in parietal bone compared to wild-type mice which show a higher elastic modulus of the frontal bone than the parietal bone

• frontal bone is more porous, showing less trabecular bone and larger lacunae at P10

• however, no difference in the elastic modulus of parietal bone is seen

abnormal sphenoid bone morphology ( J:92433 )

• skull base shortening is mainly in the sphenoid region

• at E14.5 chondrocyte proliferation in the basisphenoid-basioccipital synchondrosis is decreased, however by E16.5 proliferation had returned to normal

decreased molar number ( J:92433 )

• one molar is missing at 4 weeks

malocclusion ( J:92433 )

• a few heterozygotes display a lateral deviation of the nasal area resulting in malocclusion and feeding impairment

short maxilla ( J:92433 )

• at 4 weeks the maxilla is shorter than normal

domed cranium ( J:92433 )

• rounding is the result of shortening on the rostrocaudal axis

short face ( J:92433 )

• heterozygotes display a shortened face

skeleton

abnormal frontal bone morphology ( J:235329 )

• elastic modulus of the frontal bone is lower than in wild-type mice at P10 and P20 and is lower than in parietal bone compared to wild-type mice which show a higher elastic modulus of the frontal bone than the parietal bone

• frontal bone is more porous, showing less trabecular bone and larger lacunae at P10

• however, no difference in the elastic modulus of parietal bone is seen

abnormal sphenoid bone morphology ( J:92433 )

• skull base shortening is mainly in the sphenoid region

• at E14.5 chondrocyte proliferation in the basisphenoid-basioccipital synchondrosis is decreased, however by E16.5 proliferation had returned to normal

decreased molar number ( J:92433 )

• one molar is missing at 4 weeks

malocclusion ( J:92433 )

• a few heterozygotes display a lateral deviation of the nasal area resulting in malocclusion and feeding impairment

short maxilla ( J:92433 )

• at 4 weeks the maxilla is shorter than normal

domed cranium ( J:92433 )

• rounding is the result of shortening on the rostrocaudal axis

increased osteoblast cell number ( J:92433 )

• significantly more osteoblasts are seen in the long bones

premature cranial suture closure ( J:92433 )

• at 4 weeks the coronal sutures are fused, the lamboid sutures partially fused, and the saggital sutures only partially separable

premature coronal suture closure ( J:92433 , J:235329 )

• at E16.5 increased overlap of the frontal and parietal bones (coronal suture) is seen (J:92433)

• at E14.5 increased proliferation of osteoprogenitors is seen in the frontal and parietal bone fronts of the coronal suture, however by E16.5 proliferation had returned to normal (J:92433)

• early fusion of the coronal suture joining the parietal and frontal bone (J:235329)

vision/eye

exophthalmos ( J:92433 )

• protruding eyes are seen

ocular hypertelorism ( J:92433 )

• widely spaced eyes are seen

growth/size/body

decreased molar number ( J:92433 )

• one molar is missing at 4 weeks

malocclusion ( J:92433 )

• a few heterozygotes display a lateral deviation of the nasal area resulting in malocclusion and feeding impairment

short face ( J:92433 )

• heterozygotes display a shortened face

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Crouzon syndrome		DOID:2339	OMIM:123500	J:92433 , J:235329

Genotype
MGI:4440857

cn12

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

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:4440856

cn13

• Allelic Composition: Fgfr2^tm2Ewj/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: B6.Cg-Fgfr2^tm2Ewj Tg(EIIa-cre)C5379Lmgd

Skeletal abnormalities in Fgfr2^tm2Ewj/Fgfr2⁺ Tg(EIIa-cre)C5379Lmgd/0 mice

mortality/aging

postnatal lethality, complete penetrance ( J:158773 )

• almost half of all mice die within 24 to 36 hours of birth

• most mice die within 2 weeks of birth with very few surviving to 3 weeks

skeleton

abnormal cranial suture morphology ( J:158773 )

• mice exhibit a patent inter-premaxillary suture with fusion of the premaxilla-maxillary sutures unlike wild-type mice

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

abnormal lambdoid suture morphology ( J:158773 )

• with proximate osteogenic fronts and cellular disorganization at P0

abnormal sagittal suture morphology ( J:158773 )

• at E16.5 to P0, mice exhibit ectopic cartilage at the sagittal suture unlike wild-type mice

short basicranium ( J:158773 )

• the anterior and overall length of the cranial base is decreased compared to in 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 )

abnormal maxillary zygomatic process morphology ( J:158773 )

• the zygomatic process of the maxilla and malar bone are fused unlike in wild-type mice

short maxilla ( J:158773 )

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice and cre-recombined Fgfr2^tm1Ewj heterozygotes

abnormal zygomatic bone morphology ( J:158773 )

• the zygomatic process of the maxilla and malar bone are fused unlike in wild-type mice

domed cranium ( J:158773 )

short humerus ( J:158773 )

• at P10

short radius ( J:158773 )

• at P10

short femur ( J:158773 )

• at P10

short tibia ( J:158773 )

• at P10

abnormal sternum morphology ( J:158773 )

• at P0, all mice exhibit bony fusions of the sternum unlike wild-type mice

abnormal skeleton development ( 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

• at E17.5 to P0, the physis hypertrophic zone is disorganized compared to in wild-type mice

enhanced osteoblast differentiation ( J:158773 )

• as determined by marker expression at E19, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

synostosis ( J:158773 )

abnormal skeleton physiology ( J:158773 )

increased osteoblast proliferation ( J:158773 )

• at E19, osteoblast proliferation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

premature coronal suture closure ( J:158773 )

• mice exhibit unilateral or bilateral coronal synostosis unlike wild-type mice

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

craniofacial

abnormal cranial suture morphology ( J:158773 )

• mice exhibit a patent inter-premaxillary suture with fusion of the premaxilla-maxillary sutures unlike wild-type mice

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

abnormal lambdoid suture morphology ( J:158773 )

• with proximate osteogenic fronts and cellular disorganization at P0

abnormal sagittal suture morphology ( J:158773 )

• at E16.5 to P0, mice exhibit ectopic cartilage at the sagittal suture unlike wild-type mice

short basicranium ( J:158773 )

• the anterior and overall length of the cranial base is decreased compared to in 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 )

abnormal maxillary zygomatic process morphology ( J:158773 )

• the zygomatic process of the maxilla and malar bone are fused unlike in wild-type mice

short maxilla ( J:158773 )

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice and cre-recombined Fgfr2^tm1Ewj heterozygotes

abnormal zygomatic bone morphology ( J:158773 )

• the zygomatic process of the maxilla and malar bone are fused unlike in wild-type mice

domed cranium ( J:158773 )

abnormal palatal shelf fusion at midline ( J:158773 )

• from E15.5 to P0, all mice exhibit bilaterally incomplete fusion at the junction of the primary and secondary palatal shelves unlike in wild-type mice

• the midline suture between the horizontal plates of the palatine bones is patent unlike in wild-type mice

• in 9 of 10 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 3 of 7 wild-type mice

decreased palatal length ( J:158773 )

growth/size/body

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice and cre-recombined Fgfr2^tm1Ewj heterozygotes

abnormal palatal shelf fusion at midline ( J:158773 )

• from E15.5 to P0, all mice exhibit bilaterally incomplete fusion at the junction of the primary and secondary palatal shelves unlike in wild-type mice

• the midline suture between the horizontal plates of the palatine bones is patent unlike in wild-type mice

• in 9 of 10 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 3 of 7 wild-type mice

decreased palatal length ( J:158773 )

decreased body weight ( J:158773 )

• beginning at P5

postnatal growth retardation ( J:158773 )

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:158773 )

• from E15.5 to P0, all mice exhibit bilaterally incomplete fusion at the junction of the primary and secondary palatal shelves unlike in wild-type mice

• the midline suture between the horizontal plates of the palatine bones is patent unlike in wild-type mice

• in 9 of 10 mice the suture between the horizontal plate of the palatine bone and the palatal shelf of the maxilla is patent compared with 3 of 7 wild-type mice

decreased palatal length ( J:158773 )

limbs/digits/tail

short humerus ( J:158773 )

• at P10

short radius ( J:158773 )

• at P10

short femur ( J:158773 )

• at P10

short tibia ( J:158773 )

• at P10

cellular

enhanced osteoblast differentiation ( J:158773 )

• as determined by marker expression at E19, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

increased osteoblast proliferation ( J:158773 )

• at E19, 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

respiratory system

short nasal bone ( J:158773 )

• the nasal region is shorter than in wild-type mice and cre-recombined Fgfr2^tm1Ewj heterozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:158773

Genotype
MGI:6116892

cn14

• Allelic Composition: Fgfr2^tm1Dor/Fgfr2⁺; Fgfr3^tm6.1Cxd/Fgfr3^tm6.1Cxd; Foxg1^tm1(cre)Skm/Foxg1⁺; Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Frs3^tm1Jheb/Frs3^tm1Jheb
• Genetic Background: involves: 129

cellular

cellular phenotype ( J:242687 )

N • cell survival and cell division at E8.75 according to mitotic marker p-HH3 immunoreactivity

nervous system

nervous system phenotype ( J:242687 )

N • brain morphology at E12.5

Genotype
MGI:3775811

cn15

• Allelic Composition: Fgfr2^tm2Dsn/Fgfr2⁺; Tg(Pgk1-cre)1Lni/0
• Genetic Background: involves: 129 * 129X1/SvJ * BALB/c * C57BL/6

Submandibular gland is hypoplastic in Fgfr2^tm2Dsn/Fgfr2⁺ Tg(Pgk1-cre)1Lni/0, Fgf10^tm1Wss/Fgf10⁺, and Fgf10^tm1Wss/Fgf10⁺ Fgfr2^tm2Dsn/Fgfr2⁺ Tg(Pgk1-cre)1Lni/0 mice

endocrine/exocrine glands

submandibular gland hypoplasia ( J:119849 )

digestive/alimentary system

submandibular gland hypoplasia ( J:119849 )

Genotype
MGI:3775807

cn16

• Allelic Composition: Fgf10^tm1Wss/Fgf10⁺; Fgfr2^tm2Dsn/Fgfr2⁺; Tg(Pgk1-cre)1Lni/0
• Genetic Background: involves: 129 * 129X1/SvJ * BALB/c * C57BL/6

Submandibular gland is hypoplastic in Fgfr2^tm2Dsn/Fgfr2⁺ Tg(Pgk1-cre)1Lni/0, Fgf10^tm1Wss/Fgf10⁺, and Fgf10^tm1Wss/Fgf10⁺ Fgfr2^tm2Dsn/Fgfr2⁺ Tg(Pgk1-cre)1Lni/0 mice

endocrine/exocrine glands

abnormal submandibular duct morphology ( J:119849 )

• submandibular salivary glands exhibit fewer ducts and terminal buds than either single heterozygous mutant

decreased submandibular gland size ( J:119849 )

• submandibular salivary glands are smaller than either single heterozygous mutant

digestive/alimentary system

abnormal submandibular duct morphology ( J:119849 )

• submandibular salivary glands exhibit fewer ducts and terminal buds than either single heterozygous mutant

decreased submandibular gland size ( J:119849 )

• submandibular salivary glands are smaller than either single heterozygous mutant

Genotype
MGI:3813483

cn17

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1.1Jpa; Fgfr2^tm1Dor/Fgfr2⁺; Twist2^tm1(cre)Dor/Twist2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

digestive/alimentary system

abnormal small intestine morphology ( J:139005 )

• there is about a 15% reduction in the length of the small intestine at E18.5 compared to controls

Genotype
MGI:3604025

cn18

• 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

Genotype
MGI:5438670

cn19

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2⁺; Tg(Pax3-cre)1Joe/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

renal/urinary system

renal/urinary system phenotype ( J:107078 )

N • mice exhibit normal-appearing kidneys after birth

N • kidneys exhibit normal cortical and medullary structures at E16.5 and remain normal throughout embryonic development

Genotype
MGI:6415681

cn20

• Allelic Composition: Fgfr2^tm3Cxd/Fgfr2⁺; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * SJL

craniofacial

abnormal cranium morphology ( J:286452 )

• in the skull of 4-week old mice, about 5% linear distances are shortened by over 5% but no linear distance is shortened by over 10%

• in the skull of 8-week old mice, about 4% linear distances are increased by over 5%

• the dorsoventral height of caudal skulls is slightly increased and the mediolateral breadth is not affected

• however, mice show no changes in bone volume or bone volume ratio of calvarial bone

short nasal bone ( J:286452 )

• skulls show mildly shortened nasal bone, with the length of the nasal bone decreased by 10% along the rostrocaudal axis in 4-week oldmice but no changes in 8-week old mice

nervous system

abnormal brain size ( J:286452 )

• the rostrocaudal length and dorsoventral height on caudal brain is increased, with a 5.3% increase in dorsoventral height

skeleton

abnormal cranium morphology ( J:286452 )

• in the skull of 4-week old mice, about 5% linear distances are shortened by over 5% but no linear distance is shortened by over 10%

• in the skull of 8-week old mice, about 4% linear distances are increased by over 5%

• the dorsoventral height of caudal skulls is slightly increased and the mediolateral breadth is not affected

• however, mice show no changes in bone volume or bone volume ratio of calvarial bone

short nasal bone ( J:286452 )

• skulls show mildly shortened nasal bone, with the length of the nasal bone decreased by 10% along the rostrocaudal axis in 4-week oldmice but no changes in 8-week old mice

respiratory system

short nasal bone ( J:286452 )

• skulls show mildly shortened nasal bone, with the length of the nasal bone decreased by 10% along the rostrocaudal axis in 4-week oldmice but no changes in 8-week old mice

growth/size/body

short nasal bone ( J:286452 )

• skulls show mildly shortened nasal bone, with the length of the nasal bone decreased by 10% along the rostrocaudal axis in 4-week oldmice but no changes in 8-week old mice

Genotype
MGI:6415627

cn21

• Allelic Composition: Fgfr2^tm3Cxd/Fgfr2⁺; Tg(Col2a1-cre)1Xya/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

craniofacial

abnormal cranium morphology ( J:286452 )

• 8-week old skulls show less malformation than 4-week old skulls

• the distance of the paired anterior zygoma is increased by 11.2% and 5.4% in 4- and 8-week old mice, respectively

• the distance between two lacrimal bones is increased by 9.4% in 4-week old mice and shows no changes in 8-week old mice

• the linear distances between the intersection of interparietal and occipital bones at the midline and the posterior palate are decreased 6.4% and 6.6% in 4- and 8-week old mice, respectively

wide metopic suture ( J:286452 )

wide sagittal suture ( J:286452 )

abnormal basicranium morphology ( J:286452 )

• mice show growth disturbance in the cranial base by P14

premature presphenoid synchondrosis closure ( J:286452 )

abnormal sphenooccipital synchondrosis ( J:286452 )

• P3 mice show shortened sphenooccipital synchondroses

premature sphenooccipital synchondrosis closure ( J:286452 )

abnormal cranial cavity morphology ( J:286452 )

• 4-week old mice show rostrocaudally shortened, but dorsoventrally increased cranial cavity, indicating a dorsoventrally increased and rostrocaudally shortened brain

decreased cranium length ( J:286452 )

• shortened skull length at 4 weeks of age

• approximately 58% linear distances in the cranium are shortened by over 5%, 33% distances exhibit less than 5% shortening, and 9% distances show over 5% increases in 4-week old mice

abnormal neurocranium morphology ( J:286452 )

• the length of the lateral neurocranium is decreased 10.2% and the width of the caudal neurocranium is increased by 5.5% in 4-week old mice

• the neurocranium is not reduced along the rostro-caudal axis and has no change along the medial-lateral axis in 8-week old mice

abnormal basioccipital bone morphology ( J:286452 )

• shortened basioccipital bone

abnormal basisphenoid bone morphology ( J:286452 )

• shortened basisphenoid bone

abnormal frontal bone morphology ( J:286452 )

• the breadth of the frontal bone is mildly increased by 5.4% in 4-week old mice

• the breadth of frontal bone shows no changes in 8-week old mice

short frontal bone ( J:286452 )

• the length of the frontal bone is mildly decreased by 5.9% in 4-week old mice

short zygomatic arch ( J:286452 )

shallow orbits ( J:286452 )

abnormal maxillary frontal process morphology ( J:286452 )

• frontal processes of the maxilla are shortened by 13.9% in 4-week old mice

• frontal processes of the maxilla are shortened by 9.2% in 8-week old mice

• the parietal frontal process of the maxilla is decreased by 7.2% in 8-week old mice

short premaxilla ( J:286452 )

• the premaxilla length is decreased by 9.3% in 4-week old mice

• the premaxilla length is reduced 11.2% in 8-week old mice

short maxilla ( J:286452 )

• maxilla length is decreased by 7.5% in 4-week old mice

• maxilla length is decreased by 8.7% in 8-week old mice

abnormal nasal bone morphology ( J:286452 )

• abnormal nasal bone at 8 weeks of age

short nasal bone ( J:286452 )

• the length of the nasal bone is decreased 13.6% in 4-week old mice

• the length of the nasal bone is decreased 12.5% in 8-week old mice

short zygomatic bone ( J:286452 )

• the zygomatic bone is shortened by 21.2% in 4-week old mice

• zygomatic bone is shortened by 9.3% in 8-week old mice

abnormal midface morphology ( J:286452 )

• 8-week old mice show a less severe midfacial shape than 4-week old mice

growth/size/body

abnormal nasal bone morphology ( J:286452 )

• abnormal nasal bone at 8 weeks of age

short nasal bone ( J:286452 )

• the length of the nasal bone is decreased 13.6% in 4-week old mice

• the length of the nasal bone is decreased 12.5% in 8-week old mice

abnormal midface morphology ( J:286452 )

• 8-week old mice show a less severe midfacial shape than 4-week old mice

skeleton

abnormal cranium morphology ( J:286452 )

• 8-week old skulls show less malformation than 4-week old skulls

• the distance of the paired anterior zygoma is increased by 11.2% and 5.4% in 4- and 8-week old mice, respectively

• the distance between two lacrimal bones is increased by 9.4% in 4-week old mice and shows no changes in 8-week old mice

• the linear distances between the intersection of interparietal and occipital bones at the midline and the posterior palate are decreased 6.4% and 6.6% in 4- and 8-week old mice, respectively

wide metopic suture ( J:286452 )

wide sagittal suture ( J:286452 )

abnormal basicranium morphology ( J:286452 )

• mice show growth disturbance in the cranial base by P14

premature presphenoid synchondrosis closure ( J:286452 )

abnormal sphenooccipital synchondrosis ( J:286452 )

• P3 mice show shortened sphenooccipital synchondroses

premature sphenooccipital synchondrosis closure ( J:286452 )

abnormal cranial cavity morphology ( J:286452 )

• 4-week old mice show rostrocaudally shortened, but dorsoventrally increased cranial cavity, indicating a dorsoventrally increased and rostrocaudally shortened brain

decreased cranium length ( J:286452 )

• shortened skull length at 4 weeks of age

• approximately 58% linear distances in the cranium are shortened by over 5%, 33% distances exhibit less than 5% shortening, and 9% distances show over 5% increases in 4-week old mice

abnormal neurocranium morphology ( J:286452 )

• the length of the lateral neurocranium is decreased 10.2% and the width of the caudal neurocranium is increased by 5.5% in 4-week old mice

• the neurocranium is not reduced along the rostro-caudal axis and has no change along the medial-lateral axis in 8-week old mice

abnormal basioccipital bone morphology ( J:286452 )

• shortened basioccipital bone

abnormal basisphenoid bone morphology ( J:286452 )

• shortened basisphenoid bone

abnormal frontal bone morphology ( J:286452 )

• the breadth of the frontal bone is mildly increased by 5.4% in 4-week old mice

• the breadth of frontal bone shows no changes in 8-week old mice

short frontal bone ( J:286452 )

• the length of the frontal bone is mildly decreased by 5.9% in 4-week old mice

short zygomatic arch ( J:286452 )

shallow orbits ( J:286452 )

abnormal maxillary frontal process morphology ( J:286452 )

• frontal processes of the maxilla are shortened by 13.9% in 4-week old mice

• frontal processes of the maxilla are shortened by 9.2% in 8-week old mice

• the parietal frontal process of the maxilla is decreased by 7.2% in 8-week old mice

short premaxilla ( J:286452 )

• the premaxilla length is decreased by 9.3% in 4-week old mice

• the premaxilla length is reduced 11.2% in 8-week old mice

short maxilla ( J:286452 )

• maxilla length is decreased by 7.5% in 4-week old mice

• maxilla length is decreased by 8.7% in 8-week old mice

abnormal nasal bone morphology ( J:286452 )

• abnormal nasal bone at 8 weeks of age

short nasal bone ( J:286452 )

• the length of the nasal bone is decreased 13.6% in 4-week old mice

• the length of the nasal bone is decreased 12.5% in 8-week old mice

short zygomatic bone ( J:286452 )

• the zygomatic bone is shortened by 21.2% in 4-week old mice

• zygomatic bone is shortened by 9.3% in 8-week old mice

decreased bone volume ( J:286452 )

• bone volume is decreased in calvarial bone due to the rostrocaudally shortened skull, but not change in bone volume ratio is seen

premature coronal suture closure ( J:286452 )

• premature closure of coronal sutures in P3 mice

vision/eye

shallow orbits ( J:286452 )

ocular hypertelorism ( J:286452 )

respiratory system

abnormal nasal bone morphology ( J:286452 )

• abnormal nasal bone at 8 weeks of age

short nasal bone ( J:286452 )

• the length of the nasal bone is decreased 13.6% in 4-week old mice

• the length of the nasal bone is decreased 12.5% in 8-week old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:286452

Genotype
MGI:5790180

cn22

• Allelic Composition: Fgfr2^tm2Cxd/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

craniofacial

wide intermaxillary suture ( J:228708 )

• widening of the intermaxillary suture

abnormal presphenoid bone morphology ( J:228708 )

• increase in cartilaginous appearance of the presphenoid bone indicating reduced ossification of this bone

abnormal zygomatic arch morphology ( J:228708 )

• fusion of the zygomatic arch at P0

short nasal bone ( J:228708 )

• foreshortening of the nasal bone

abnormal palatine bone morphology ( J:228708 )

• severe palatal bone dysplasia at P0 associated with a widening of the intermaxillary suture

• dysplasia of the palatine bone involves anterior curvature of the vertical processes and an overall porous appearance

domed cranium ( J:228708 )

midface hypoplasia ( J:228708 )

growth/size/body

short nasal bone ( J:228708 )

• foreshortening of the nasal bone

midface hypoplasia ( J:228708 )

skeleton

wide intermaxillary suture ( J:228708 )

• widening of the intermaxillary suture

abnormal presphenoid bone morphology ( J:228708 )

• increase in cartilaginous appearance of the presphenoid bone indicating reduced ossification of this bone

abnormal zygomatic arch morphology ( J:228708 )

• fusion of the zygomatic arch at P0

short nasal bone ( J:228708 )

• foreshortening of the nasal bone

abnormal palatine bone morphology ( J:228708 )

• severe palatal bone dysplasia at P0 associated with a widening of the intermaxillary suture

• dysplasia of the palatine bone involves anterior curvature of the vertical processes and an overall porous appearance

domed cranium ( J:228708 )

abnormal trabecular bone morphology ( J:228708 )

• poor cancellous bone formation of the cranial base

premature coronal suture closure ( J:228708 )

• fusion of the coronal suture at P0

premature facial suture closure ( J:228708 )

• facial suture synostosis at P0, with fusion of the premaxillary-maxillary, nasal-frontal, and maxillary-palatine sutures

premature maxillary-premaxillary suture closure ( J:228708 )

• fusion of the premaxillary-maxillary suture at P0

premature palatomaxillary suture closure ( J:228708 )

• fusion of the maxillary-palatine suture at P0

premature frontonasal suture closure ( J:228708 )

• fusion of the nasal-frontal suture at P0

respiratory system

short nasal bone ( J:228708 )

• foreshortening of the nasal bone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:228708

Genotype
MGI:3604078

cn23

• Allelic Composition: Fgfr2^tm2Cxd/Fgfr2⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:101385 )

• mutants with severe cranial abnormalities die within 20 days of birth, less severely affected mutants survive to adulthood

growth/size/body

malocclusion ( J:101385 )

midface hypoplasia ( J:101385 )

• midface hypoplasia

decreased embryo size ( J:101385 )

• severely affected mutants are very small compared to wild-type mice, less severely affected mutants are 70-80% of the size of wild-type littermates

skeleton

abnormal cranium morphology ( J:101385 )

• some adults have asymmetrical skulls; however no obvious hand/foot abnormalities are seen

abnormal cranial suture morphology ( J:101385 )

• at P1 and P8 increased apoptosis is seen with the highest levels seen in the parietal and frontal bones; however no significant difference in osteoblast proliferation (at E16.5, E18.5, P1, P5, and P8) or differentiation (at E18.5, P1, and P18) is seen in the sutures

abnormal sagittal suture morphology ( J:101385 )

• development of the sagittal suture is slightly delayed

decreased cranium height ( J:101385 )

• significant shortening of the anterior-posterior axis

abnormal neurocranium morphology ( J:101385 )

• calvarial bone formation is decreased

thin frontal bone ( J:101385 )

• the frontal bone is thinner and at P1 and P8 increased apoptosis is seen

thin parietal bone ( J:101385 )

• the parietal bone is thinner and at P1 and P8 increased apoptosis is seen

short presphenoid bone ( J:101385 )

• the presphenoid bone is significantly shorter

malocclusion ( J:101385 )

domed cranium ( J:101385 )

abnormal long bone epiphyseal plate proliferative zone ( J:101385 )

• after P10 some mutants have slightly shorter columns of proliferating chondrocytes

premature cranial suture closure ( J:101385 )

• craniosynostosis is most pronounced in the coronal suture

premature coronal suture closure ( J:101385 )

• premature closure of the coronal suture is first seen around E18.5 with more significant overlap between the osteogenic fronts developing over time and fewer mesenchymal cells are found in the coronal suture at birth

vision/eye

ocular hypertelorism ( J:101385 )

reproductive system

female infertility ( J:101385 )

♀ • all surviving females are sterile

reduced male fertility ( J:101385 )

♂ • only 1 male generated 2 litters when mated with a wild-type female

craniofacial

abnormal craniofacial morphology ( J:101385 )

• cranial abnormalities vary in severity and the severely affected mutants die postnatally

abnormal cranium morphology ( J:101385 )

• some adults have asymmetrical skulls; however no obvious hand/foot abnormalities are seen

abnormal cranial suture morphology ( J:101385 )

• at P1 and P8 increased apoptosis is seen with the highest levels seen in the parietal and frontal bones; however no significant difference in osteoblast proliferation (at E16.5, E18.5, P1, P5, and P8) or differentiation (at E18.5, P1, and P18) is seen in the sutures

abnormal sagittal suture morphology ( J:101385 )

• development of the sagittal suture is slightly delayed

decreased cranium height ( J:101385 )

• significant shortening of the anterior-posterior axis

abnormal neurocranium morphology ( J:101385 )

• calvarial bone formation is decreased

thin frontal bone ( J:101385 )

• the frontal bone is thinner and at P1 and P8 increased apoptosis is seen

thin parietal bone ( J:101385 )

• the parietal bone is thinner and at P1 and P8 increased apoptosis is seen

short presphenoid bone ( J:101385 )

• the presphenoid bone is significantly shorter

malocclusion ( J:101385 )

domed cranium ( J:101385 )

midface hypoplasia ( J:101385 )

• midface hypoplasia

embryo

decreased embryo size ( J:101385 )

• severely affected mutants are very small compared to wild-type mice, less severely affected mutants are 70-80% of the size of wild-type littermates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acrocephalosyndactylia		DOID:12960	OMIM:101200	J:101385

Genotype
MGI:3525679

cn24

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2⁺; Tg(Hoxb7-cre)5526Cmb/0
• Genetic Background: involves: FVB/N

renal/urinary system

renal/urinary system phenotype ( J:95018 )

N • normal kidneys and no apparent renal abnormalities

Genotype
MGI:3702560

cx25

• Allelic Composition: Fgfr2^tm1.1Dor/Fgfr2⁺; Spry2^tm1.1Mrt/Spry2^tm1.1Mrt
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ

craniofacial

craniofacial phenotype ( J:119280 )

N • unlike in mice homozygous for the Spry2 allele alone, no diastema tooth formation is seen

Genotype
MGI:6416132

cx26

• Allelic Composition: Fgfr2^tm3.1Lni/Fgfr2⁺; Hmgcs2^em1Wilh/Hmgcs2^em1Wilh
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

reproductive system phenotype ( J:285178 )

♂N • testes development is similar to controls

Genotype
MGI:6162253

cx27

• Allelic Composition: Fgfr2^tm1.1Dor/Oat^rhg
• Genetic Background: involves: AKR/J * C57BL/6J * C57BL/6JEi * FVB/N

normal phenotype

no abnormal phenotype detected ( J:213842 )

• double heterozygotes have normal vibrissae, fur and overall growth rate