Mouse Genome Informatics
cn1
    Ext1tm1Yama/Ext1tm1Yama
B6.129S5-Ext1tm1Yama
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• 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 Tgfb2tm1Doe homozygous cells

cellular
• 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 Tgfb2tm1Doe homozygous cells


Mouse Genome Informatics
cn2
    Ext1tm1Yama/Ext1tm1Yama
Tg(Wnt1-cre)11Rth/0

B6.Cg-Ext1tm1Yama Tg(Wnt1-cre)11Rth
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die within the first day of birth

vision/eye
• mice exhibit eye morphology defects
• however, lens thickness is normal
• 58% of mutant mice exhibit ciliary body coloboma
• at E18.5, 99% of mutant mice exhibit ventral iris coloboma
• the corneal stroma lacks collagen staining unlike in wild-type mice

craniofacial

hearing/vestibular/ear

embryogenesis
• 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

cellular
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Peters Anomaly 604229 J:152572


Mouse Genome Informatics
cn3
    Ext1tm1Yama/Ext1+
Tg(Wnt1-cre)11Rth/0
Tgfb2tm1Doe/Tgfb2+

B6.Cg-Tgfb2tm1Doe Ext1tm1Yama Tg(Wnt1-cre)11Rth
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice survive into adulthood (J:152572)

vision/eye
• mice exhibit defects in components of the aqueous drainage system
• however, the iridocorneal angle is normal
• the trabecular beam contains fewer cells than in wild-type mice
• mice exhibit ocular hypertension unlike single heterozygotes


Mouse Genome Informatics
cn4
    Ext1tm1Yama/Ext1+
Slit2tm1Matl/Slit2tm1Matl
Tg(Nes-cre)1Kln/0

involves: 129S2/SvPas * 129S5/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 59-67% of retinal axons project ectopically into the contralateral optic nerve

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


Mouse Genome Informatics
cn5
    Ext1tm1Yama/Ext1tm1Yama
Tg(Camk2a-cre)2834Lusc/0

involves: 129S5/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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
• 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
• in the open-field test, mutants exhibit higher levels of locomotor activity
• 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
• in the hot plate test, mutants exhibit shorter latency to respond to thermal stimuli indicating sensory hypersensitivity
• mutants exhibit reduced nest-building activity
• 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
• 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

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

nervous system
• 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
• mutants exhibit depressed input-output curve of compound excitatory postsynaptic currents (EPSCs) in the basolateral amygdala
• mutants exhibit reduced AMPA receptor-mediated synaptic strength in basolateral amygdala neurons
• 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
OMIM IDRef(s)
Autism 209850 J:180302


Mouse Genome Informatics
cn6
    Ext1tm1Yama/Ext1tm1Yama
Tg(Nes-cre)1Kln/0

involves: 129S5/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die within 1 day of birth

nervous system
• 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
• differentiation of the caudal midbrain and cerebellum initiated but failed to form the distinct inferior colliculus and cerebellum
• absence of the major commissure tracts
• overall size and thickness is reduced
• cell proliferation in the cortex is reduced by about 30% compared with controls

cellular
• 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


Mouse Genome Informatics
cn7
    Ext1tm1Yama/Ext1tm1Yama
Tg(Col2a1-cre/ERT)KA3Smac/0

involves: 129S5/SvEvBrd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• without tamoxifen treatment, mice exhibit multiple hereditary exostose-like skeletal defects unlike wild-type mice
• mice exhibit subluxation/dislocation of the radius unlike wild-type mice
• 92% of mice exhibit bowing of the radius and subluxation/dislocation of the radial head unlike wild-type mice
• at P14, mice exhibit an increase in the width of the distal radius compared to wild-type mice
• at P14, mice exhibit an increase in the width of the distal ulna compared to wild-type mice
• in 58% of mice
• 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
• mice exhibit mild abnormalities of the joint cartilage unlike wild-type mice
• 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
• mild
• at P21, mice exhibit small cartilaginous islands for in the epiphysis unlike in wild-type mice

tumorigenesis
• 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

limbs/digits/tail
• mice exhibit bowing of the forearm unlike wild-type mice
• mice exhibit subluxation/dislocation of the radius unlike wild-type mice
• 92% of mice exhibit bowing of the radius and subluxation/dislocation of the radial head unlike wild-type mice
• at P14, mice exhibit an increase in the width of the distal radius compared to wild-type mice
• at P14, mice exhibit an increase in the width of the distal ulna compared to wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Exostoses, Multiple, Type I 133700 J:161395