Mouse Genome Informatics
cn1
    Fgfr2tm1Ewj/Fgfr2+
Tg(EIIa-cre)C5379Lmgd/0

B6.Cg-Fgfr2tm1Ewj Tg(EIIa-cre)C5379Lmgd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• 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
• the inter-premaxillary suture appears patent unlike in wild-type mice
• the suture between the horizontal plate of the palatine bone and palatal process of the maxilla is fused unlike in wild-type mice
• skull height is increased compared to in wild-type mice
• mice exhibit shorter maxilla than wild-type and cre-recombined Fgfr2tm2Ewj heterozygotes
• the nasal region is shorter than in wild-type mice
• coronal sutures exhibit increased osteogenic differentiation and accelerated bone growth compared to in wild-type mice
• however, apoptosis rates at coronal sutures is normal
• as determined by marker expression, osteoblast differentiation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice
• mice exhibit coronal synostosis unlike wild-type mice
• at P0, mice exhibit coronal suture presynostosis or synostosis unlike wild-type mice
• osteoblast proliferation at the chondro-osseuous junction and the metaphysis is increased compared to in wild-type mice

craniofacial
• 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
• the inter-premaxillary suture appears patent unlike in wild-type mice
• the suture between the horizontal plate of the palatine bone and palatal process of the maxilla is fused unlike in wild-type mice
• skull height is increased compared to in wild-type mice
• mice exhibit shorter maxilla than wild-type and cre-recombined Fgfr2tm2Ewj heterozygotes
• the nasal region is shorter than in wild-type mice
• the most posterior portion of the palate is reduced compared to in wild-type mice
• 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
• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2tm2Ewj heterozygotes

digestive/alimentary system
• the most posterior portion of the palate is reduced compared to in wild-type mice
• 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
• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2tm2Ewj heterozygotes

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

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

growth/size/body
• the most posterior portion of the palate is reduced compared to in wild-type mice
• 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
• mice exhibit shorter palate than wild-type and cre-recombined Fgfr2tm2Ewj heterozygotes


Mouse Genome Informatics
cn2
    Fgfr2tm1Ewj/Fgfr2+
Tg(EIIa-cre)C5379Lmgd/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants with complete recombination die within 24 -36 hours of birth; however, 2 mutants with only partial recombination survived to adulthood

respiratory system
• presence of proteinaceous fluid in the alveoli is observed
• multifocal and acute bronchiolectasis with mild dilation of the bronchioles are seen in mutants with complete recombination
• a complete cartilage sleeve surrounds the trachea in mutants with complete recombination
• seen in mutants with complete recombination
• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination
• moderate and diffuse atelectasis with lack of alveolar expansion and the presence of proteinaceous fluid in the alveoli is observed

skeleton
• 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
• 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
• 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
• at P1 in mutants with complete recombination synostosis with osteoid deposition is seen
• at P1 in mutants with complete recombination synostosis with osteoid deposition is seen
• 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
• 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
• 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
• structures of the neurocranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age
• the interparietal bone is compressed superiorly at the lambdoid suture in mutants with only partial recombination at 10 months of age
• the parietal bones have an obvious superior bulge in mutants with only partial recombination at 10 months of age
• the temporal process of the zygomatic bone is fused to the zygomatic process of the temporal bone in mutants with complete recombination
• dysmorphic angular process in mutants with only partial recombination at 10 months of age
• the mandible is very small in mutants with only partial recombination at 10 months of age
• the frontal process of the maxilla has an abnormally large sinus and bowing of the medial wall and the zygomatic process is bowed more laterally in mutants with only partial recombination at 10 months of age
• seen in mutants with complete recombination
• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age
• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones
• the nasal cartilage is thickened
• a complete cartilage sleeve surrounds the trachea in mutants with complete recombination
• 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
• in mutants with complete recombination, the hypertrophic zone of the growth plate of the long bones is subtly irregular
• seen in 6 of 9 mutants with complete recombination (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)

growth/size/body
• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination
• at birth in mutants with complete recombination body weight is about 83% that of wild-type littermates
• in mutants with only partial recombination at 10 months of age body weight is 29% that of wild-type littermates
• in mutants with only partial recombination at 10 months of age head shape is abnormal
• structures of the face are about 40-50% smaller in mutants with only partial recombination at 10 months of age
• malformations of the palate are seen in all mutants
• in mutants with only partial recombination at 10 months of age body length is 68% that of wild-type littermates

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

immune system
• diffuse lymphoid necrosis and apoptosis of variable severity is seen in mutants with complete recombination
• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones
• multifocal and acute bronchiolectasis with mild dilation of the bronchioles are seen in mutants with complete recombination

nervous system
• 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
• mild hydroencephaly with enlarged ventricles is present in mutants with complete recombination
• in 2 of 10 mice
• cerebral height is increased compared to in wild-type mice
• mice exhibit cerebral asymmetry to varying degrees compared with wild-type mice
• arched in 2 of 10 mice

craniofacial
• 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
• 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
• at P1 in mutants with complete recombination synostosis with osteoid deposition is seen
• at P1 in mutants with complete recombination synostosis with osteoid deposition is seen
• 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
• 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
• 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
• structures of the neurocranium are about 30-40% smaller in mutants with only partial recombination at 10 months of age
• the interparietal bone is compressed superiorly at the lambdoid suture in mutants with only partial recombination at 10 months of age
• the parietal bones have an obvious superior bulge in mutants with only partial recombination at 10 months of age
• the temporal process of the zygomatic bone is fused to the zygomatic process of the temporal bone in mutants with complete recombination
• dysmorphic angular process in mutants with only partial recombination at 10 months of age
• the mandible is very small in mutants with only partial recombination at 10 months of age
• the frontal process of the maxilla has an abnormally large sinus and bowing of the medial wall and the zygomatic process is bowed more laterally in mutants with only partial recombination at 10 months of age
• seen in mutants with complete recombination
• dysmorphology of the nasal bones is seen in mutants with only partial recombination at 10 months of age
• structures of the face are about 40-50% smaller in mutants with only partial recombination at 10 months of age
• malformations of the palate are seen in all mutants

hematopoietic system
• diffuse lymphoid necrosis and apoptosis of variable severity is seen in mutants with complete recombination
• in mutants with complete recombination, a decrease in osteoclast numbers is seen at the chondro-osseous junction in long bones

digestive/alimentary system
• malformations of the palate are seen in all mutants
• aerophagia with mild distension of the stomach and intestine is seen in mutants with complete recombination

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

homeostasis/metabolism
• presence of proteinaceous fluid in the alveoli is observed

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

Mouse Models of Human Disease
OMIM IDRef(s)
Apert Syndrome 101200 J:101174 , J:156940