Phenotypes associated with this allele

• Allele Symbol: Ext1^tm1Yama
• Allele Name: targeted mutation 1, Yu Yamaguchi
• Allele ID: MGI:2682061
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ext1^tm1Yama/Ext1^tm1Yama	B6.129S5-Ext1^tm1Yama	MGI:4360748
cn2	Ext1^tm1Yama/Ext1^tm1Yama H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	B6.Cg-H2az2^Tg(Wnt1-cre)11Rth Ext1^tm1Yama	MGI:4360747
cn3	Ext1^tm1Yama/Ext1^+ H2az2^Tg(Wnt1-cre)11Rth/H2az2^+ Tgfb2^tm1Doe/Tgfb2^+	B6.Cg-Tgfb2^tm1Doe H2az2^Tg(Wnt1-cre)11Rth Ext1^tm1Yama	MGI:4360749
cn4	Ext1^tm1Yama/Ext1^+ Slit2^tm1Matl/Slit2^tm1Matl Tg(Nes-cre)1Kln/0	involves: 129S2/SvPas * 129S5/SvEvBrd * C57BL/6 * SJL	MGI:2682063
cn5	Ext1^tm1Yama/Ext1^tm1Yama Acan^tm1(cre/ERT2)Crm/Acan^+	involves: 129S5/SvEvBrd * 129S6/SvEvTac * C57BL/6NCrl	MGI:6101205
cn6	Ext1^tm1Yama/Ext1^tm1Yama Tg(Camk2a-cre)2834Lusc/0	involves: 129S5/SvEvBrd * C57BL/6	MGI:5316488
cn7	Ext1^tm1Yama/Ext1^tm1Yama Tg(Nes-cre)1Kln/0	involves: 129S5/SvEvBrd * C57BL/6 * SJL	MGI:2682062
cn8	Ext1^tm1Yama/Ext1^tm1Yama Tg(Col2a1-cre/ERT)KA3Smac/0	involves: 129S5/SvEvBrd * FVB/N	MGI:4818630

Genotype
MGI:4360748

cn1

• Allelic Composition: Ext1^tm1Yama/Ext1^tm1Yama
• Genetic Background: B6.129S5-Ext1^tm1Yama

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

embryo

decreased cranial neural crest cell proliferation ( J:152572 )

• periocular neural crest cells transfected with an adeno-cre exhibit reduced proliferation compared with similarly treated wild-type cells but not as much as in Tgfb2^tm1Doe homozygous cells

cellular

decreased cranial neural crest cell proliferation ( J:152572 )

• periocular neural crest cells transfected with an adeno-cre exhibit reduced proliferation compared with similarly treated wild-type cells but not as much as in Tgfb2^tm1Doe homozygous cells

Genotype
MGI:4360747

cn2

• Allelic Composition: Ext1^tm1Yama/Ext1^tm1Yama; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: B6.Cg-H2az2^{Tg(Wnt1-cre)11Rth} Ext1^tm1Yama

Craniofacial malformation in Ext1^tm1Yama/Ext1^tm1YamaH2az2^{Tg(Wnt1-cre)11Rth}/0 mice

mortality/aging

neonatal lethality, complete penetrance ( J:152572 )

• all mice die within the first day of birth

vision/eye

abnormal eye morphology ( J:152572 )

• mice exhibit eye morphology defects

• however, lens thickness is normal

abnormal iridocorneal angle ( J:152572 )

• reduced

ciliary body coloboma ( J:152572 )

• 58% of mutant mice exhibit ciliary body coloboma

iris coloboma ( J:152572 )

• at E18.5, 99% of mutant mice exhibit ventral iris coloboma

decreased cornea thickness ( J:152572 )

abnormal cornea stroma morphology ( J:152572 )

• the corneal stroma lacks collagen staining unlike in wild-type mice

decreased eye anterior chamber depth ( J:152572 )

• shallow anterior chamber

absent eyelids ( J:152572 )

craniofacial

abnormal craniofacial morphology ( J:152572 )

absent hard palate ( J:152572 )

cleft secondary palate ( J:152572 )

hearing/vestibular/ear

abnormal ear morphology ( J:152572 )

• at E18.5

embryo

decreased cranial neural crest cell proliferation ( J:152572 )

• at E15.5, neural crest cell proliferation is reduced compared to in wild-type mice

• however, neural crest cell migration into the periocular mesenchyme at E11.5 and levels of apoptosis are normal

digestive/alimentary system

absent hard palate ( J:152572 )

cleft secondary palate ( J:152572 )

cellular

decreased cranial neural crest cell proliferation ( J:152572 )

• at E15.5, neural crest cell proliferation is reduced compared to in wild-type mice

• however, neural crest cell migration into the periocular mesenchyme at E11.5 and levels of apoptosis are normal

growth/size/body

absent hard palate ( J:152572 )

cleft secondary palate ( J:152572 )

Genotype
MGI:4360749

cn3

• Allelic Composition: Ext1^tm1Yama/Ext1⁺; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺; Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: B6.Cg-Tgfb2^tm1Doe H2az2^{Tg(Wnt1-cre)11Rth} Ext1^tm1Yama

Thin cornea and iridocorneal dysgenesis in Ext1^tm1Yama/Ext1⁺ H2az2^{Tg(Wnt1-cre)11Rth}/0 Tgfb2^tm1Doe/Tgfb2⁺ mice

mortality/aging

mortality/aging ( J:152572 )

N • mice survive into adulthood

vision/eye

abnormal aqueous drainage system morphology ( J:152572 )

• mice exhibit defects in components of the aqueous drainage system

• however, the iridocorneal angle is normal

abnormal canal of Schlemm morphology ( J:152572 )

abnormal trabecular meshwork morphology ( J:152572 )

• the trabecular beam contains fewer cells than in wild-type mice

ocular hypertension ( J:152572 )

• mice exhibit ocular hypertension unlike single heterozygotes

Genotype
MGI:2682063

cn4

• Allelic Composition: Ext1^tm1Yama/Ext1⁺; Slit2^tm1Matl/Slit2^tm1Matl; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S2/SvPas * 129S5/SvEvBrd * C57BL/6 * SJL

nervous system

abnormal axon guidance ( J:86465 )

• 59-67% of retinal axons project ectopically into the contralateral optic nerve

cellular

abnormal axon guidance ( J:86465 )

• 59-67% of retinal axons project ectopically into the contralateral optic nerve

Genotype
MGI:6101205

cn5

• Allelic Composition: Ext1^tm1Yama/Ext1^tm1Yama; Acan^{tm1(cre/ERT2)Crm}/Acan⁺
• Genetic Background: involves: 129S5/SvEvBrd * 129S6/SvEvTac * C57BL/6NCrl

neoplasm

increased osteochondroma incidence ( J:242977 )

• mice injected with tamoxifen at P28 or P35 form large osteochondromas along synchondroses in the cranial base and along growth plates of long bones by 6-8 weeks after injection

• systemic treatment of tamoxifen-injected with mice a BMP signaling antagonist, LDN-193189 reduces osteochondroma development and growth

skeleton

increased osteochondroma incidence ( J:242977 )

• mice injected with tamoxifen at P28 or P35 form large osteochondromas along synchondroses in the cranial base and along growth plates of long bones by 6-8 weeks after injection

• systemic treatment of tamoxifen-injected with mice a BMP signaling antagonist, LDN-193189 reduces osteochondroma development and growth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary multiple exostoses		DOID:206	OMIM:133700 OMIM:133701 OMIM:600209	J:242977

Genotype
MGI:5316488

cn6

• Allelic Composition: Ext1^tm1Yama/Ext1^tm1Yama; Tg(Camk2a-cre)2834Lusc/0
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6

behavior/neurological

decreased anxiety-related response ( J:182220 )

• in the elevated plus maze, mutants spend more than half the session time on the open arms and moved freely on them compared to wild-type mice that remain mostly on the closed arms, indicating reduced fear of height

• in the light/dark box text, mutants spent more time in the brightly illuminated space than wild-type mice, although the number of transitions between light and dark spaces did not differ

• in the open-field test, mutants spend a longer time in the central area than wild-type mice and exhibit higher levels of locomotor activity, indicating reduced fear of open spaces

decreased fear-related response ( J:182220 )

• in the elevated plus maze, mutants spend more than half the session time on the open arms and moved freely on them compared to wild-type mice that remain mostly on the closed arms, indicating reduced fear of height

• in the light/dark box text, mutants spent more time in the brightly illuminated space than wild-type mice, although the number of transitions between light and dark spaces did not differ

• in the open-field test, mutants spend a longer time in the central area than wild-type mice and exhibit higher levels of locomotor activity, indicating reduced fear of open spaces

increased locomotor activity ( J:182220 )

• in the open-field test, mutants exhibit higher levels of locomotor activity

increased stereotypic behavior ( J:182220 )

• in the hole-board test, while wild-type mice explore different holes in a random or successive manner, mutants show a tendency towards making repeated head-dips into the same hole, indicating stereotyped dip behavior; occurrence of stereotypic dip was significantly greater, however the total number of head-dips did not differ from wild-type

• mutants show a tendency to perform consecutive head-dips of more than 4 repetitions, a behavior not seen in wild-type mice

• however, mutants do not exhibit spontaneous stereotypic behavior such as jumping, circling, paw flapping or self-grooming

decreased thermal nociceptive threshold ( J:182220 )

• in the hot plate test, mutants exhibit shorter latency to respond to thermal stimuli indicating sensory hypersensitivity

abnormal nest building behavior ( J:182220 )

• mutants exhibit reduced nest-building activity

abnormal social investigation ( J:182220 )

• in a separation-reunion test with siblings, mutants show less interactions with siblings after reunion

• in the resident-intruder test, while wild-type mice explore the intruder extensively, mutants seldom chase the intruder and instead frequently show behaviors of avoidance, such as freezing and moving away

• in the social dominance tube test, mutants almost always retreat out of the tube and lose

decreased vocalization ( J:182220 )

• ultrasonic vocalization emitted by mutants is reduced significantly in terms of number, duration, and amplitude of calls in response to female odor compared to wild-type mice

• complexity of ultrasonic vocalization is reduced compared to wild-type mice

nervous system

abnormal synaptic transmission ( J:182220 )

• excitatory synaptic transmission is altered in amygdala neurons

• however, mutants do not exhibit overt abnormalities in the overall morphology of the amygdala or in the morphology of dendritic arbors and spines in pyramidal neurons of the basolateral amygdala

abnormal excitatory postsynaptic currents ( J:182220 )

• mutants exhibit depressed input-output curve of compound excitatory postsynaptic currents (EPSCs) in the basolateral amygdala

reduced AMPA-mediated synaptic currents ( J:182220 )

• mutants exhibit reduced AMPA receptor-mediated synaptic strength in basolateral amygdala neurons

abnormal miniature excitatory postsynaptic currents ( J:182220 )

• frequency of mEPSCs is reduced in mutant basolateral amygdala pyramidal neurons

• amplitude of mEPSCs is reduced in basolateral amygdala neurons, indicating that AMPA receptor-mediated postsynaptic activity is reduced

• however, neither the rising nor the decay of time of mEPSCs is altered, indicating that channel kinetics of AMPA receptors is preserved

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:182220

Genotype
MGI:2682062

cn7

• Allelic Composition: Ext1^tm1Yama/Ext1^tm1Yama; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6 * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:86465 )

• all mice die within 1 day of birth

nervous system

abnormal axon guidance ( J:86465 )

• 60-67% of retinal axons project ectopically into the contralateral optic nerve

• axons from the cortex fail to approach the midline and instead extend ventrally unlike wild-type axons that turn to the midline and cross toward the contralateral side

• axons emerging from the external capsule extend straight toward the ventral surface of the forebrain instead of turning towards the midline to form the anterior commissure

abnormal brain development ( J:86465 )

• differentiation of the caudal midbrain and cerebellum initiated but failed to form the distinct inferior colliculus and cerebellum

abnormal brain commissure morphology ( J:86465 )

• absence of the major commissure tracts

absent corpus callosum ( J:86465 )

absent hippocampal commissure ( J:86465 )

absent anterior commissure ( J:86465 )

absent inferior colliculus ( J:86465 )

abnormal cerebral cortex morphology ( J:86465 )

• overall size and thickness is reduced

• cell proliferation in the cortex is reduced by about 30% compared with controls

thin cerebral cortex ( J:86465 )

absent olfactory bulb ( J:86465 )

absent cerebellum ( J:86465 )

cellular

abnormal axon guidance ( J:86465 )

• 60-67% of retinal axons project ectopically into the contralateral optic nerve

• axons from the cortex fail to approach the midline and instead extend ventrally unlike wild-type axons that turn to the midline and cross toward the contralateral side

• axons emerging from the external capsule extend straight toward the ventral surface of the forebrain instead of turning towards the midline to form the anterior commissure

Genotype
MGI:4818630

cn8

• Allelic Composition: Ext1^tm1Yama/Ext1^tm1Yama; Tg(Col2a1-cre/ERT)KA3Smac/0
• Genetic Background: involves: 129S5/SvEvBrd * FVB/N

skeleton

abnormal skeleton morphology ( J:161395 )

• without tamoxifen treatment, mice exhibit multiple hereditary exostose-like skeletal defects unlike wild-type mice

dislocated radius head ( J:161395 )

• 92% of mice exhibit bowing of the radius and subluxation/dislocation of the radial head unlike wild-type mice

bowed radius ( J:161395 )

• 92% of mice exhibit bowing of the radius

increased diameter of radius ( J:161395 )

• at P14, mice exhibit an increase in the width of the distal radius compared to wild-type mice

increased diameter of ulna ( J:161395 )

• at P14, mice exhibit an increase in the width of the distal ulna compared to wild-type mice

increased osteochondroma incidence ( J:161395 )

• without tamoxifen treatment, all mice develop osteochondroma in the humerus, radius, ulna, digits, femur, tibia, fibula, vertebrae, and rib bones unlike wild-type mice

• at P7 to P28 in the ribs

• at P14 in the distal femur

• osteochondromas resemble ectopic growth plates rather than true neoplasm

scoliosis ( J:161395 )

• in 58% of mice

exostosis ( J:161395 )

• mice exhibit bony protrusions with a cartilage cap in the wrist, fibula, shoulder, and rib unlike wild-type mice

• at P14, mice exhibit exostosis unlike wild-type mice

• at P28, mice exhibit multiple protrusions closely resembling osteochondroma unlike in wild-type mice

abnormal cartilage morphology ( J:161395 )

• mice exhibit mild abnormalities of the joint cartilage unlike wild-type mice

abnormal cartilage development ( J:161395 )

• at P14,formation of cartilage occurs in abnormal location compared to in wild-type mice

• at P21, mice exhibit overgrowth and deformity of the cartilage compared with wild-type mice and small cartilaginous islands for in the epiphysis

abnormal epiphyseal plate morphology ( J:161395 )

• mild

• at P21, mice exhibit small cartilaginous islands for in the epiphysis unlike in wild-type mice

neoplasm

increased osteochondroma incidence ( J:161395 )

• without tamoxifen treatment, all mice develop osteochondroma in the humerus, radius, ulna, digits, femur, tibia, fibula, vertebrae, and rib bones unlike wild-type mice

• at P7 to P28 in the ribs

• at P14 in the distal femur

• osteochondromas resemble ectopic growth plates rather than true neoplasm

growth/size/body

decreased body height ( J:161395 )

limbs/digits/tail

abnormal forelimb morphology ( J:161395 )

• mice exhibit bowing of the forearm unlike wild-type mice

dislocated radius head ( J:161395 )

• 92% of mice exhibit bowing of the radius and subluxation/dislocation of the radial head unlike wild-type mice

bowed radius ( J:161395 )

• 92% of mice exhibit bowing of the radius

increased diameter of radius ( J:161395 )

• at P14, mice exhibit an increase in the width of the distal radius compared to wild-type mice

increased diameter of ulna ( J:161395 )

• at P14, mice exhibit an increase in the width of the distal ulna compared to wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary multiple exostoses		DOID:206	OMIM:133700 OMIM:133701 OMIM:600209	J:161395