Phenotypes associated with this allele

• Allele Symbol: Fgfr2^tm1.1Dsn
• Allele Name: targeted mutation 1.1, Clive Dickson
• Allele ID: MGI:2153811
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fgfr2^tm1.1Dsn/Fgfr2^tm1.1Dsn	involves: 129P2/OlaHsd	MGI:2676258
hm2	Fgfr2^tm1.1Dsn/Fgfr2^tm1.1Dsn	involves: 129P2/OlaHsd * C57BL/6	MGI:2173367
ht3	Fgfr2^tm1.1Dsn/Fgfr2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:2173369

Genotype
MGI:2676258

hm1

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

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

Palatal abnormalities in Fgfr2^tm1.1Dsn/Fgfr2^tm1.1Dsn and Fgf10^tm1Wss/Fgf10^tm1Wss mice

craniofacial

craniofacial phenotype ( J:145189 )

N • in vitro, E14.5 palatal explants implanted with FGF18-soaked beads show the expected ectopic induction of Runx1 expression in the palatal epithelium surrounding the FGF18 beads

N • in vivo, Runx1 mRNA expression is not downregulated in the tip of the fusing palatal epithelium at E15.5

abnormal palate morphology ( J:90909 )

• palates are short, squared in shape

abnormal palatal mesenchymal cell proliferation ( J:90909 )

• mesenchymal proliferation in the palate is reduced at E12 and E13 by 12-32%

abnormal secondary palate development ( J:90909 )

• palatal epithelium is thin and lacks stratification and in some cases the epithelial covering at the tip of the palatal projection has disintegrated and the underlying mesenchymal cells have broken through into the oral cavity

• epithelial cell proliferation is reduced in all areas of the palate at E12 and E13

• mesenchymal proliferation in the palate is reduced at E12 and E13 by 12-32%

• exhibit an increase in apoptotic cells in the palate at E13

• however, cultured palates from mutant mice fuse in vitro

palatal shelf fusion with tongue or mandible ( J:90909 )

• exhibit epithelial fusions between the nasal surface of the palate and the tongue, as well as the oral surface of the palate and the mandible

decreased palatal length ( J:90909 )

absent palatal rugae ( J:90909 )

• absent

cleft secondary palate ( J:90909 )

• exhibit a complete, wide cleft of the secondary palate; palate abnormalities first noted at E13

• do not have finger-like projections lateral to the tongue

abnormal tongue morphology ( J:90909 )

• exhibit isolated epithelial outgrowths on the dorsal surface of the tongue

tongue ankylosis ( J:90909 )

• exhibit partial ankylosis of the tongue, with defective epithelialization between the floor of the mouth and tongue

abnormal nasal gland morphology ( J:237227 )

• the maxillary sinus gland is completely absent

abnormal lateral nasal gland morphology ( J:237227 )

• the lateral nasal glands (LNG2,3,5) are present but show reduced branching

• lateral nasal gland 4, which normally forms underneath the nasal cartilage capsule, is completely absent at E18.5

• the Steno's gland (lateral nasal gland 1) is completely absent

respiratory system

abnormal nasal gland morphology ( J:237227 )

• the maxillary sinus gland is completely absent

abnormal lateral nasal gland morphology ( J:237227 )

• the lateral nasal glands (LNG2,3,5) are present but show reduced branching

• lateral nasal gland 4, which normally forms underneath the nasal cartilage capsule, is completely absent at E18.5

• the Steno's gland (lateral nasal gland 1) is completely absent

digestive/alimentary system

abnormal palate morphology ( J:90909 )

• palates are short, squared in shape

abnormal palatal mesenchymal cell proliferation ( J:90909 )

• mesenchymal proliferation in the palate is reduced at E12 and E13 by 12-32%

abnormal secondary palate development ( J:90909 )

• palatal epithelium is thin and lacks stratification and in some cases the epithelial covering at the tip of the palatal projection has disintegrated and the underlying mesenchymal cells have broken through into the oral cavity

• epithelial cell proliferation is reduced in all areas of the palate at E12 and E13

• mesenchymal proliferation in the palate is reduced at E12 and E13 by 12-32%

• exhibit an increase in apoptotic cells in the palate at E13

• however, cultured palates from mutant mice fuse in vitro

palatal shelf fusion with tongue or mandible ( J:90909 )

• exhibit epithelial fusions between the nasal surface of the palate and the tongue, as well as the oral surface of the palate and the mandible

decreased palatal length ( J:90909 )

absent palatal rugae ( J:90909 )

• absent

cleft secondary palate ( J:90909 )

• exhibit a complete, wide cleft of the secondary palate; palate abnormalities first noted at E13

• do not have finger-like projections lateral to the tongue

abnormal tongue morphology ( J:90909 )

• exhibit isolated epithelial outgrowths on the dorsal surface of the tongue

tongue ankylosis ( J:90909 )

• exhibit partial ankylosis of the tongue, with defective epithelialization between the floor of the mouth and tongue

endocrine/exocrine glands

abnormal nasal gland morphology ( J:237227 )

• the maxillary sinus gland is completely absent

abnormal lateral nasal gland morphology ( J:237227 )

• the lateral nasal glands (LNG2,3,5) are present but show reduced branching

• lateral nasal gland 4, which normally forms underneath the nasal cartilage capsule, is completely absent at E18.5

• the Steno's gland (lateral nasal gland 1) is completely absent

abnormal pancreas development ( J:82083 )

• pancreatic ductal branching (2-fold reduction in the number of ductal lumens at E15.5) and duct cell proliferation are reduced, however both exocrine and endocrine pancreatic differentiation occurs normally

small pancreas ( J:82083 )

• pancreas is smaller during embryogenesis

growth/size/body

abnormal palate morphology ( J:90909 )

• palates are short, squared in shape

abnormal palatal mesenchymal cell proliferation ( J:90909 )

• mesenchymal proliferation in the palate is reduced at E12 and E13 by 12-32%

abnormal secondary palate development ( J:90909 )

• palatal epithelium is thin and lacks stratification and in some cases the epithelial covering at the tip of the palatal projection has disintegrated and the underlying mesenchymal cells have broken through into the oral cavity

• epithelial cell proliferation is reduced in all areas of the palate at E12 and E13

• mesenchymal proliferation in the palate is reduced at E12 and E13 by 12-32%

• exhibit an increase in apoptotic cells in the palate at E13

• however, cultured palates from mutant mice fuse in vitro

palatal shelf fusion with tongue or mandible ( J:90909 )

• exhibit epithelial fusions between the nasal surface of the palate and the tongue, as well as the oral surface of the palate and the mandible

decreased palatal length ( J:90909 )

absent palatal rugae ( J:90909 )

• absent

cleft secondary palate ( J:90909 )

• exhibit a complete, wide cleft of the secondary palate; palate abnormalities first noted at E13

• do not have finger-like projections lateral to the tongue

abnormal tongue morphology ( J:90909 )

• exhibit isolated epithelial outgrowths on the dorsal surface of the tongue

tongue ankylosis ( J:90909 )

• exhibit partial ankylosis of the tongue, with defective epithelialization between the floor of the mouth and tongue

abnormal nasal gland morphology ( J:237227 )

• the maxillary sinus gland is completely absent

abnormal lateral nasal gland morphology ( J:237227 )

• the lateral nasal glands (LNG2,3,5) are present but show reduced branching

• lateral nasal gland 4, which normally forms underneath the nasal cartilage capsule, is completely absent at E18.5

• the Steno's gland (lateral nasal gland 1) is completely absent

Genotype
MGI:2173367

hm2

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

Submandibular gland abnormalities in Fgf10^tm1Ska/Fgf10^tm1Ska and Fgfr2^tm1.1Dsn/Fgfr2^tm1.1Dsn mice at E12.5

mortality/aging

perinatal lethality, complete penetrance ( J:59285 )

• die at birth due to failure of lung formation

growth/size/body

arrest of tooth development ( J:59285 )

• teeth do not develop normally and fail to progress beyond the bud stage

cleft palate ( J:59285 )

inner ear cyst ( J:59285 )

• the whole inner ear is generally cystic in appearance

decreased body size ( J:59285 )

respiratory system

abnormal lung development ( J:59285 )

• defective lung development is apparent at E10.5

• E12.5 embryos show a finger of mesenchyme surrounded by a single layer of epithelium which exhibits extensive apoptosis by E14.5

impaired branching involved in trachea morphogenesis ( J:59285 )

• at E10.5, primary bronchi are absent due to failure of tracheal bifurcation

absent lungs ( J:59285 , J:92361 )

• mice fail to form lungs (J:59285)

• no lungs present at E18.5 (J:59285)

limbs/digits/tail

absent forelimb ( J:59285 , J:92361 )

absent hindlimb ( J:59285 , J:92361 )

abnormal limb development ( J:59285 )

• E10.5 embryos show the beginning of limb bud initiation but no thickening of the epithelium characteristic of an apical endodermal ridge

• exhibit extensive apoptosis in the presumptive limb bud mesoderm and some in the overlying epithelium

caudal vertebral fusion ( J:59285 )

• tail at E16.5 shows malformed and fused caudal vertebrae

curly tail ( J:59285 , J:92361 )

craniofacial

arrest of tooth development ( J:59285 )

• teeth do not develop normally and fail to progress beyond the bud stage

domed cranium ( J:59285 )

cleft palate ( J:59285 )

endocrine/exocrine glands

abnormal salivary gland morphology ( J:59285 )

• deficiency in salivary gland formation

absent submandibular gland ( J:119849 )

• the submandibular salivary gland is entirely absent at E13.5

submandibular gland hypoplasia ( J:119849 )

• the submandibular salivary gland is severely hypoplastic at E12.5, showing an extremely small initial bud

absent adenohypophysis ( J:59285 )

• the anterior pituitary is absent, however the infundibular recess and its derivative, the pars nervosa, are present and appear normal

abnormal pituitary gland development ( J:59285 )

abnormal Rathke's pouch apoptosis ( J:59285 )

• at E10.5, Rathke's pouch epithelium exhibits numerous apoptotc cells as shown by TUNEL analysis

abnormal Rathke's pouch development ( J:59285 )

• at E10.5, Rathke's pouch is poorly formed with fewer cell layers forming the walls of the diverticulum and shows widespread apoptosis

absent Rathke's pouch ( J:59285 )

• Rathke's pouch is absent at E14.5

abnormal mammary gland bud morphology ( J:73434 )

♀ • embryos transiently develop only mammary bud 4 at E11.5; however, the epithelium of mammary bud 4 undergoes extensive apoptosis at E12.5, and by E13 and E14.5, bud 4 is absent

♀ • at E16.5, no mammary bud development is detected in mutant skin, while five pairs are clearly seen in wild-type controls

abnormal mammary placode morphology ( J:109476 )

♀ • all placodes (1, 2, 3, 5) except 4 are absent along the mammary line

♀ • when flanks from Fgf10-deficient mice are cultured with FGF10 beads, placode formation is rescued

absent mammary gland ( J:73434 )

♀ • a mammary bud arising from placode 4 forms transiently at E11.5 and is then lost within a day through apoptosis; the other 4 mammary placodes (1, 2, 3, and 5) are absent

hearing/vestibular/ear

inner ear cyst ( J:59285 )

• the whole inner ear is generally cystic in appearance

small otic vesicle ( J:72516 )

• otic vesicles at E10 and E11 are smaller than controls

• do not observe fusion of the canal plates at E13-14

abnormal cochlea morphology ( J:72516 )

• the cochlea is disrupted

abnormal cochlear sensory epithelium morphology ( J:72516 )

• exhibit rudimentary sensory epithelia

abnormal semicircular canal morphology ( J:59285 , J:72516 )

• semicircular canal formation is abnormal (J:59285)

• at E13 and E14, do not observe elongation of the semicircular ducts (J:72516)

abnormal membranous labyrinth morphology ( J:72516 )

• at E18, the cochleovestibular membraneous labyrinth is severely disrupted and is replaced by cystic cavities or chambers that are lined by simple epithelium

abnormal endolymphatic duct morphology ( J:59285 , J:72516 )

• some mutants show failure of endolymphatic duct formation at E10.5 (J:59285)

• about 50% of otocyts between E11 and E14 do not show any signs of initiation of endolymphatic duct formation (J:72516)

• at E13 and E14, do not observe elongation of the endolymphatic ducts (J:72516)

abnormal otic capsule morphology ( J:72516 )

small otic capsule ( J:59285 )

• otic capsules are greatly reduced in size

vision/eye

absent eyelids ( J:59285 )

• eyes are open due to an apparent absence of eyelids

digestive/alimentary system

cleft palate ( J:59285 )

abnormal cecum development ( J:87411 )

• development of the cecum is altered, such that a cecal bud forms but is much smaller at E12.5 and the epithelial layer does not invade the mesenchymal layer

• at E13.5, ceca show mesenchymal buds that fail to continue development and show no progressive elongation of the structure

cecal atresia ( J:92361 )

• 100% show cecal atresia with absence of epithelial and smooth muscular layers

abnormal rectum morphology ( J:92361 )

• anorectal malformation characterized by an absence of rectum in the pelvis, anorectal discontinuity, shortened perineal body and perineal hypospodias

absent rectum ( J:92361 )

• absence of rectum in the pelvis

abnormal perineum morphology ( J:92361 )

• shortened perineal body and perineal hypospodias

abnormal salivary gland morphology ( J:59285 )

• deficiency in salivary gland formation

absent submandibular gland ( J:119849 )

• the submandibular salivary gland is entirely absent at E13.5

submandibular gland hypoplasia ( J:119849 )

• the submandibular salivary gland is severely hypoplastic at E12.5, showing an extremely small initial bud

abnormal stomach morphology ( J:59285 )

• stomach exhibits some differences in tissue architecture compared to controls

small stomach ( J:59285 )

nervous system

absent adenohypophysis ( J:59285 )

• the anterior pituitary is absent, however the infundibular recess and its derivative, the pars nervosa, are present and appear normal

abnormal pituitary gland development ( J:59285 )

abnormal Rathke's pouch apoptosis ( J:59285 )

• at E10.5, Rathke's pouch epithelium exhibits numerous apoptotc cells as shown by TUNEL analysis

abnormal Rathke's pouch development ( J:59285 )

• at E10.5, Rathke's pouch is poorly formed with fewer cell layers forming the walls of the diverticulum and shows widespread apoptosis

absent Rathke's pouch ( J:59285 )

• Rathke's pouch is absent at E14.5

abnormal vestibulocochlear ganglion morphology ( J:72516 )

• although initial delamination and migration of neuronal precursors is seen at E10, this process and the formation of the cochleovestibular ganglion is severely retarded at E11

• large number of cochleovestibular neurons are undergoing apoptosis at E13

• neurons of the rudimentary cochleovestibular ganglion eminate fibers toward the periphery but the neurites do not penetrate the otic epithelium

skeleton

arrest of tooth development ( J:59285 )

• teeth do not develop normally and fail to progress beyond the bud stage

domed cranium ( J:59285 )

caudal vertebral fusion ( J:59285 )

• tail at E16.5 shows malformed and fused caudal vertebrae

abnormal clavicle morphology ( J:59285 )

• the clavicle is fused to the coracoid process

absent acromion ( J:59285 )

small scapula ( J:59285 )

• the scapula, particularly the blade and coracoid process, is greatly reduced in size and the acromion fails to form

abnormal pelvic girdle bone morphology ( J:59285 )

• the pelvic girdle is severely malformed

abnormal ilium morphology ( J:59285 )

• exhibit only a rudimentary ileum

abnormal ischium morphology ( J:59285 )

• exhibit only a rudimentary ischium and absent ischial rami

absent pubis ( J:59285 )

• absent pubis

premature squamoparietal suture closure ( J:59285 )

• premature suture between the parietal and squamous temporal bones

pigmentation

decreased skin pigmentation ( J:59285 )

• skin is lighter in color

reproductive system

abnormal perineum morphology ( J:92361 )

• shortened perineal body and perineal hypospodias

renal/urinary system

perineal hypospadia ( J:92361 )

• perineal hypospadias

integument

abnormal mammary gland bud morphology ( J:73434 )

♀ • embryos transiently develop only mammary bud 4 at E11.5; however, the epithelium of mammary bud 4 undergoes extensive apoptosis at E12.5, and by E13 and E14.5, bud 4 is absent

♀ • at E16.5, no mammary bud development is detected in mutant skin, while five pairs are clearly seen in wild-type controls

abnormal mammary placode morphology ( J:109476 )

♀ • all placodes (1, 2, 3, 5) except 4 are absent along the mammary line

♀ • when flanks from Fgf10-deficient mice are cultured with FGF10 beads, placode formation is rescued

absent mammary gland ( J:73434 )

♀ • a mammary bud arising from placode 4 forms transiently at E11.5 and is then lost within a day through apoptosis; the other 4 mammary placodes (1, 2, 3, and 5) are absent

absent hypodermis muscle layer ( J:59285 )

• show no discernible panniculus carnosus muscle layer that normally lies beneath the dermis

thin dermal layer ( J:59285 )

• the different stratified layers of the dermis are thinner and appear less well organized

abnormal epidermis stratum basale morphology ( J:59285 , J:109476 )

• the basal keratinocyte layer between the hair follicles is particularly thin (J:59285)

• exhibit a decrease in the number of cycling cells in the basal layer, however the outer hair follicle sheath appears normal (J:59285)

• in E11.5-11.75 embryos, cells of the stratum germinativum are cuboidal rather than cylindrical and formation of the periderm is impaired (J:109476)

thin epidermis ( J:59285 )

• the different stratified layers of the epidermis are thinner and appear less well organized, however epidermal differentiation appears normal

translucent skin ( J:59285 )

decreased skin pigmentation ( J:59285 )

• skin is lighter in color

thin skin ( J:59285 )

muscle

absent hypodermis muscle layer ( J:59285 )

• show no discernible panniculus carnosus muscle layer that normally lies beneath the dermis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
intestinal atresia		DOID:10486		J:92361

Genotype
MGI:2173369

ht3

• 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