Mouse Genome Informatics
cn1
    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
cn2
    Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Ptpn11tm1.1Rbns/Ptpn11tm1.1Rbns
Tg(Wnt1-cre)11Rth/0

B6.Cg-Ptpn11tm1.1Rbns Gt(ROSA)26Sortm1Sor Tg(Wnt1-cre)11Rth
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• at E12.5, the number of neural crest cells in the outflow tract cushions are less than in wild-type mice
• at E17.5, the number of neural crest cells in the proximal outflow tract is less than in wild-type mice
• however, initial proliferation and migration are normal
• cranial neural crest cells fail to differentiate into osteoblasts unlike in wild-type mice

nervous system
• at E12.5, the number of neural crest cells in the outflow tract cushions are less than in wild-type mice
• at E17.5, the number of neural crest cells in the proximal outflow tract is less than in wild-type mice
• however, initial proliferation and migration are normal
• cranial neural crest cells fail to differentiate into osteoblasts unlike in wild-type mice

cardiovascular system
• at E12.5, the number of neural crest cells in the outflow tract cushions are less than in wild-type mice
• at E17.5, the number of neural crest cells in the proximal outflow tract is less than in wild-type mice
• however, initial proliferation and migration are normal


Mouse Genome Informatics
cn3
    Ptpn11tm1.1Rbns/Ptpn11tm1.1Rbns
Tg(Wnt1-cre)11Rth/0

B6.Cg-Ptpn11tm1.1Rbns 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
• embryo survival drops after E15.5 and no mice are born alive

craniofacial
• neural crest cell-derived mandible is dramatically ablated or completely absent
• neural crest cell-derived craniofacial bones are dramatically ablated or completely absent
• neural crest cell-derived nasal cartilage is dramatically ablated or completely absent
• small nose

cardiovascular system
• abnormal arch arteries are observed in 32% with 5 of 19 mice exhibiting malpositioning of the left carotid artery and 1 of 19 exhibiting defective left carotid artery
• mice exhibit a truncal valve containing 3 leaflets (in 90% of mice) or 4 leaflets (in 10% of mice) unlike in wild-type mice
• the truncal valve is longer and thicker than the aortic valves of wild-type mice
• however, the atrioventricular valves are normal
• all mice exhibit persistent truncus arteriosus
• 84% of heart have type II and 16% type I persistent truncus arteriosus

growth/size
• neural crest cell-derived nasal cartilage is dramatically ablated or completely absent
• small nose

hearing/vestibular/ear

respiratory system
• neural crest cell-derived nasal cartilage is dramatically ablated or completely absent

skeleton
• neural crest cell-derived mandible is dramatically ablated or completely absent
• neural crest cell-derived craniofacial bones are dramatically ablated or completely absent
• neural crest cell-derived nasal cartilage is dramatically ablated or completely absent

vision/eye

digestive/alimentary system


Mouse Genome Informatics
cn4
    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
cn5
    Tbx1tm2.1Bem/Tbx1tm2.1Bem
Tg(Wnt1-cre)11Rth/0

either: (involves: 129/Sv * C57BL/6 * C57BL/6J * CBA/J * SJL) or (involves: 129/Sv * C57BL/6J * CBA/J * CD-1 * SJL)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice exhibit no abnormalities


Mouse Genome Informatics
cn6
    Lmo4tm1Sho/Lmo4tm1Sho
Tg(Wnt1-cre)11Rth/0

either: (involves: 129/Sv * CD-1) or (involves: 129/Sv * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
N
• presphenoid bone formed properly (J:88168)


Mouse Genome Informatics
cn7
    Chd7Gt(XK403)Byg/Chd7+
Tg(Wnt1-cre)11Rth/0

either: (involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA/J) or (involves: 129P2/OlaHsd * C57BL/6J * CBA/J * CD-1)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system

craniofacial

embryogenesis


Mouse Genome Informatics
cn8
    Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

either: (involves: 129S/SvEv * C57BL/6 * CBA) or (involves: 129S/SvEv * C57BL/6 * CBA * CD-1)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E9.5 and E10.5, the cranial neural tube is open dorsally
• at E9.5 and E10.5, the isthmus (the constriction of the neural tube at the midbrain hindbrain boundary) is absent
• at E9.5 and E10.5 the brain rostral to the otic vesicle is significantly smaller

embryogenesis
• at E9.5 and E10.5, the cranial neural tube is open dorsally


Mouse Genome Informatics
cn9
    Mrgprdtm1Mjz/?
Rettm1Ddg/Rettm1Ddg
Tg(Wnt1-cre)11Rth/0

involves: 129 * 129S1/Sv * C57BL/6 * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at P14, GFP+ skin neuron projections are reduced and punctate unlike in control Mrgprdtm1Mjz Rettm1Ddg homozygotes
• however, central axonal projections in the thoracic spinal cord exhibit normal lamina specific innervation of peptidergic and nonpectidergic projections


Mouse Genome Informatics
cn10
    Mfn2tm1Dcc/Mfn2tm3Dcc
Tg(Wnt1-cre)11Rth/0

involves: 129 * 129S4/SvJaeSor * Black Swiss
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant pups are born at appropriate Mendelian ratio
• after birth, about one third of mutant mice die on postnatal day 1
• all remaining mutant mice die by P17

behavior/neurological
• mice surviving beyond P1 cannot easily regain posture when placed on their backs
• mice surviving beyond P1 display uncoordinated limb movements, and move primarily by writhing on their abdomen

growth/size
• mice surviving beyond P1 are severely runted, likely due to feeding problems secondary to their movement disorder

nervous system
• severe defect in postnatal cerebellar growth


Mouse Genome Informatics
cn11
    Rettm1Ddg/Rettm1Ddg
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• few mice survive beyond 3 weeks

digestive/alimentary system
• at P14
• enlarged at P14

nervous system
• at P14, non-peptidergic neurons are hypotrophic unlike in control Rettm1Ddg homozygotes
• in the small intestine and colon
• at P14, the dorsal root ganglia is 30% smaller than in control Rettm1Ddg homozygotes

behavior/neurological
• beginning at P3 mice develop progressive weakness

growth/size


Mouse Genome Informatics
cn12
    Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Sox11tm2.1Weg/Sox11tm2.1Weg
Sox4tm1Vlf/Sox4tm1Vlf
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• massive cell death in the branchial arches without a decrease in cell proliferation

embryogenesis
• massive cell death in the branchial arches without a decrease in cell proliferation


Mouse Genome Informatics
cn13
    Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Isl1tm2Sev/Isl1tm2Sev
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within a few hours of birth

nervous system
• cutaneous branch of the ventral ramus is absent in E14.5 embryos
• innervation of the distal limbs at E14.5 confirmed a nearly complete loss of fine cutaneous sensory fibers with only a single sensory branch innervating one side of digits 1, 2 and 5 in both the forelimb and hindlimb
• there is an increased rate of apoptosis within the trigeminal ganglia of E11.5 and E12.5 embryos
• the dorsal root ganglion (DRG) of E12.5 embryos do not express Isl1 protein
• TrkA+ neurons are lower in number starting at E12.5 and by E14.5 are less than one-third of what is found in controls
• TrkB+ neurons are also lower in number starting at E12.5 and are markedly reduced at E14.5 and birth
• TrkC+ neurons do not appear until E12.5, a delay of two days compared to controls
• the DRG of E14.5 embryos is markedly smaller than controls with a smaller number neurons found within the ganglion
• an increased rate of apoptosis is noted in the E12.5 DRG

behavior/neurological
• mice have a reduced response to a mild noxious stimulus that was applied to the skin of the trunk or limbs

integument
• mice have a reduced response to a mild noxious stimulus that was applied to the skin of the trunk or limbs


Mouse Genome Informatics
cn14
    Hdac1tm1.1Eno/Hdac1tm1.1Eno
Tg(Wnt1-cre)11Rth/?

involves: 129 * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• no abnormal phenotype is detected in skull development


Mouse Genome Informatics
cn15
    Hdac2tm1.1Eno/Hdac2tm1.1Eno
Tg(Wnt1-cre)11Rth/?

involves: 129 * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• no abnormal phenotype is detected in skull development


Mouse Genome Informatics
cn16
    Hdac8tm1.1Eno/Y
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some mice die within 4-6 hours after birth from brain hemorrhaging (J:150709)

cardiovascular system
• some mice die within 4-6 hours after birth from brain hemorrhaging (J:150709)
• hemorrhaging results from ossification defects in the skull (J:150709)

craniofacial
• ossification defects lead to the presence of soft tissues in the frontal and interparietal bone (J:150709)

nervous system
• some mice die within 4-6 hours after birth from brain hemorrhaging (J:150709)
• hemorrhaging results from ossification defects in the skull (J:150709)

skeleton
• ossification defects lead to the presence of soft tissues in the frontal and interparietal bone (J:150709)
• ossification defects lead to the presence of soft tissues in the frontal and interparietal bone and incomplete skull closure (J:150709)


Mouse Genome Informatics
cn17
    Cited2tm1Bha/Cited2tm2Bha
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• despite present in Mendelian ratios at E18.5, fewer than expected survive to weaning
• despite present in Mendelian ratios at E18.5, fewer than expected survive to weaning

nervous system
• in one mouse
• 11 of 14 mice exhibit fusion of ganglia IX and X
• 11 of 14 mice exhibit fusion of ganglia IX and X


Mouse Genome Informatics
cn18
    Dicer1tm1Bdh/Dicer1tm1Bdh
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
• discontinuance of the ascending aortic arch with the descending aorta, indicating improper pattering of the aortic arch due to a left fourth aortic arch defect
• the outflow tract does not fully septate into a pulmonary artery and aorta in some cases, resulting in the persistence of a common outflow vessel

craniofacial
• severe craniofacial defects are seen by E14.5
• although pharyngeal arches appear similar to wild-type in emergence, size and shape, expression of Dlx2 and Fgf8 are downregulated in pharyngeal arch 1
• apoptosis is increased in the first pharyngeal arch at E11.5

embryogenesis
• although pharyngeal arches appear similar to wild-type in emergence, size and shape, expression of Dlx2 and Fgf8 are downregulated in pharyngeal arch 1
• apoptosis is increased in the first pharyngeal arch at E11.5

hematopoietic system
• thymus development is absent

immune system
• thymus development is absent

nervous system
• loss of neural crest cell derived neuronal tissue from the thoracic sympathetic ganglia
• loss of neural crest cell derived neuronal tissue from the dorsal root ganglia

skeleton
• neural crest cell derived maxillary and mandibular regions of the face and frontonasal process lack cartilaginous tissue, however mesodermally derived cartilage near the base of the skull is present

endocrine/exocrine glands
• thymus development is absent

Mouse Models of Human Disease
OMIM IDRef(s)
DiGeorge Syndrome; DGS 188400 J:166758


Mouse Genome Informatics
cn19
    Dicer1tm1Bdh/Dicer1+
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• thymus development is delayed at E14.5, but by E16.5, the thymus is indistinguishable from wild-type

immune system
• thymus development is delayed at E14.5, but by E16.5, the thymus is indistinguishable from wild-type

endocrine/exocrine glands
• thymus development is delayed at E14.5, but by E16.5, the thymus is indistinguishable from wild-type


Mouse Genome Informatics
cn20
    Ctnnb1tm2Kem/Ctnnb1tm3Kba
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• differentiation of sensory neurons in the neural tube is defective
• milder defects than in conditional mutant mice homozygous for Ctnnb1tm2Kem at E12.5

craniofacial
• milder defects than in conditional mutant mice homozygous for Ctnnb1tm2Kem at E12.5

embryogenesis
N
• apical neural tube morphology is not disrupted at E12.5 (J:178971)

cellular
• differentiation of sensory neurons in the neural tube is defective


Mouse Genome Informatics
cn21
    Ctnnb1tm2Kem/Ctnnb1tm2Kem
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• disruption of apical neural tube morphology leading to migration of cells into the neural canal
• malformed telencephalic lobes at E12.5

craniofacial

embryogenesis
• disruption of apical neural tube morphology leading to migration of cells into the neural canal

cellular


Mouse Genome Informatics
cn22
    Ctnnb1tm2Kem/Ctnnb1tm3Kba
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• not developed at E10.5

craniofacial
• hypoplastic and malformed

skeleton
• hypoplastic and malformed


Mouse Genome Informatics
cn23
    Ctnnb1tm2Kem/Ctnnb1tm2Kem
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• at E12.5
• at E12.5
• rudimentary at E12.5

nervous system
• absence of midbrain structures at E10.5
• absence of hindbrain structures at E10.5

embryogenesis
• rudimentary at E12.5

skeleton
• at E12.5
• at E12.5


Mouse Genome Informatics
cn24
    Hs2st1tm1.1Je/Hs2st1tm1.1Je
Hs6st1tm1Wvc/Hs6st1tm1Wvc
Hs6st2tm1Lex/Hs6st2tm1Lex
Tg(Wnt1-cre)11Rth/0

involves: 129 * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
N
• lacrimal gland budding is preserved (J:185652)


Mouse Genome Informatics
cn25
    Ctnnb1tm2Kem/Ctnnb1tm2.1Kem
Tg(Wnt1-cre)11Rth/?

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no mutant mice are born

craniofacial
• craniofacial bones derived from neural crest cells are absent
• bones present include optic vesicle, basioccipital, exoccipital

skeleton
• craniofacial bones derived from neural crest cells are absent
• bones present include optic vesicle, basioccipital, exoccipital

nervous system
• brain morphogenesis grossly abnormal between E10.5 and 18.5
• isthmic border between midbrain and rhombencephalon not visible
• choroid plexus absent by E12.5
• by E10.5 parts of the midbrain are missing
• no discernable midbrain by E12.5
• enlarged telencephalon
• walls of cephalic vesicles thinner
• anterior hindbrain is missing by E10.5
• poorly formed connections between cranial ganglia and hindbrain
• cerebellum is missing at E12.5
• anterior hindbrain is missing by E10.5
• combined ganglion with vestibulocochlear nerve abnormal
• roots poorly formed
• hypoglossal nerve missing
• roots poorly formed
• first spinal root ganglion missing
• other spinal root ganglia severely affected as well

embryogenesis


Mouse Genome Informatics
cn26
    Nf1tm1Par/Nf1tm1Tyj
Tg(Wnt1-cre)11Rth/0

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• increase in the frequency of neural crest stem cells in the sympathetic chain, dorsal root ganglia, and sciatic nerve at E13 but not at E17 to E19

nervous system
• increase in the frequency of neural crest stem cells in the sympathetic chain, dorsal root ganglia, and sciatic nerve at E13 but not at E17 to E19


Mouse Genome Informatics
cn27
    Myocdtm1Msp/Myocdtm1Msp
Tg(Wnt1-cre)11Rth/0

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• majority of mutants die before P3

cardiovascular system
• the architecture of the neointima and tunica media of the ductus arteriosus is disturbed
• increase in fibronectin and laminin in the ductus arteriosus
• all mutants at P2 exhibit patent ductus arteriosus
• E16.5 mutants exhibit diminished expression of smooth muscle cell contractile proteins in the ductus arteriosus
• however, patterning of the cardiac outflow tract and great arteries is normal
• the smooth muscle cells of the ductus arteriosus are heterogeneous in size with a loss of spindle-like cell morphology
• the smooth muscle cells of the ductus arteriosus have relatively few myofibers and show an increase in synthetic organelles, including the rough ER and Golgi

homeostasis/metabolism
• pups become cyanotic shortly after birth

muscle
• the smooth muscle cells of the ductus arteriosus are heterogeneous in size with a loss of spindle-like cell morphology
• the smooth muscle cells of the ductus arteriosus have relatively few myofibers and show an increase in synthetic organelles, including the rough ER and Golgi

Mouse Models of Human Disease
OMIM IDRef(s)
Patent Ductus Arteriosus 607411 J:131288


Mouse Genome Informatics
cn28
    Gt(ROSA)26Sortm1(PDGFRA*)Hsc/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• coronal suture closing begins 15 days after birth and is completed by 20 days of age
• there is a premature fusion of the posterior frontal suture 5 days after birth
• by ten days after birth, fusion of the anterior frontal suture becomes evident
• the interfrontal bone is noticeably larger than controls starting at E16.5
• new borns have an overgrowth of the interfrontal bone in the anterior frontal calvaria
• the frontal bones of five day old mice are structured more trabecularly and have an increased portion of calcified bone matrix
• three-fold more osteprogenitors are actively proliferating within the frontal sutures of E19.5 fetuses compared to controls
• 1.4 fold more primary osteoblasts of calvaria tissue actively proliferate in vitro compared to controls
• all osteprogenitors from interfrontal bones differentiate into osteoblasts after three days in culture compared to only half of controls
• there is a premature fusion of the posterior frontal suture 5 days after birth
• by ten days after birth, fusion of the anterior frontal suture becomes evident
• coronal suture closing begins 15 days after birth and is completed by 20 days of age

craniofacial
• coronal suture closing begins 15 days after birth and is completed by 20 days of age
• there is a premature fusion of the posterior frontal suture 5 days after birth
• by ten days after birth, fusion of the anterior frontal suture becomes evident
• the interfrontal bone is noticeably larger than controls starting at E16.5
• new borns have an overgrowth of the interfrontal bone in the anterior frontal calvaria
• the frontal bones of five day old mice are structured more trabecularly and have an increased portion of calcified bone matrix
• a shortened craniofacial area is noticeable at one week after birth and worsens as the mice age

growth/size
• a shortened craniofacial area is noticeable at one week after birth and worsens as the mice age


Mouse Genome Informatics
cn29
    Rarbtm2Ipc/Rarbtm2Ipc
Rargtm3Ipc/Rargtm3Ipc
Tg(Wnt1-cre)11Rth/?

involves: 129/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• severe ventral rotation of the lens
• at E14.5, a thick layer of mesenchyme replaces the eyelids and cornea and a small, abnormal conjuctival sac is present
• at E10.5 and E11.5 no apoptosis is seen in dorsal and ventral cluster of cells in the periocular mesenchyme where apoptosis is seen in wild-type mice
• retrolenticular membrane resulting from the persistence and hyperplasia of the primary vitreous body
• severe shortening of the ventral retina

embryogenesis
• at E10.5 and E11.5 no apoptosis is seen in dorsal and ventral cluster of cells in the periocular mesenchyme where apoptosis is seen in wild-type mice

growth/size
• at E10.5 and E11.5 no apoptosis is seen in dorsal and ventral cluster of cells in the periocular mesenchyme where apoptosis is seen in wild-type mice


Mouse Genome Informatics
cn30
    Hoxa2tm1.1Fmr/Hoxa2tm1.1Fmr
Tg(Wnt1-cre)11Rth/0

involves: 129/Sv * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• structures derived from the second arch, including the stapes, styloid process, and lesser horns of the hyoid bone, are absent and replaced by first arch-like derived structures, including duplicated incus, malleus, and tympanic bone, transformed gonial bone, and partially duplicated Meckel's cartilage, with reverse polarity
• the lesser horns of the hyoid bone are absent
• the gonial bone appears transformed such that it is enlarged and stretches across, bridging over the two halves of the mirror duplication

hearing/vestibular/ear
• the gonial bone appears transformed such that it is enlarged and stretches across, bridging over the two halves of the mirror duplication
• duplicated tympanic bone

skeleton
• structures derived from the second arch, including the stapes, styloid process, and lesser horns of the hyoid bone, are absent and replaced by first arch-like derived structures, including duplicated incus, malleus, and tympanic bone, transformed gonial bone, and partially duplicated Meckel's cartilage, with reverse polarity
• the lesser horns of the hyoid bone are absent
• the gonial bone appears transformed such that it is enlarged and stretches across, bridging over the two halves of the mirror duplication

growth/size


Mouse Genome Informatics
cn31
    Bhlhe22tm2.1Meg/Bhlhe22tm2.1Meg
Tg(Wnt1-cre)11Rth/0

involves: 129/Sv * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice show excessive scratching in response to pruritic agent compound 48/80
• mice show excessive scratching in response to pruritic agent compound 48/80

integument
• mice show excessive scratching in response to pruritic agent compound 48/80
• animals display self-inflicted skin lesions, identical in frequency, location, and severity to those observed in Bhlhe22tm1Meg homozygotes


Mouse Genome Informatics
cn32
    Bmp4tm2(tetO-Bmp4,lacZ)Jfm/Bmp4+
Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129/Sv * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• following doxycycline treatment at E10.5 a strong reduction in rostral bony elements is seen and multiple translucent areas are seen in the skull bones
• later treatment with doxycycline has less dramatic effects on bone morphology
• reduced or absent following doxycycline treatment at E12.5
• following doxycycline treatment at E12.5
• following doxycycline treatment at E12.5
• doxycycline treatment at E11.5 or E10.5 results in a shorter mandible with a more pointed appearance
• doxycycline treatment at E13.5 results in a mandible with a more pointed appearance
• reduced following doxycycline treatment at E13.5
• following doxycycline treatment at E12.5, E11.5 or at E10.5
• doxycycline treatment at E10.5 results in a shorter maxilla with a more pointed appearance
• following doxycycline treatment at E10.5
• following doxycycline treatment at E12.5 in some mice
• following doxycycline treatment at E10.5, E12.5, or E13.5
• enlarged following doxycycline treatment at E12.5
• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
• following doxycycline treatment at E12.5
• following doxycycline treatment at E10.5 the overall shape of the head is more rounded
• shortened face following doxycycline treatment at E10.5

vision/eye
• following doxycycline treatment at E10.5 the orientation of the eyes is more anterior

respiratory system
• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5

digestive/alimentary system
• following doxycycline treatment at E12.5

skeleton
• following doxycycline treatment at E10.5 a strong reduction in rostral bony elements is seen and multiple translucent areas are seen in the skull bones
• later treatment with doxycycline has less dramatic effects on bone morphology
• reduced or absent following doxycycline treatment at E12.5
• following doxycycline treatment at E12.5
• following doxycycline treatment at E12.5
• doxycycline treatment at E11.5 or E10.5 results in a shorter mandible with a more pointed appearance
• doxycycline treatment at E13.5 results in a mandible with a more pointed appearance
• reduced following doxycycline treatment at E13.5
• following doxycycline treatment at E12.5, E11.5 or at E10.5
• doxycycline treatment at E10.5 results in a shorter maxilla with a more pointed appearance
• following doxycycline treatment at E10.5
• following doxycycline treatment at E12.5 in some mice
• following doxycycline treatment at E10.5, E12.5, or E13.5
• enlarged following doxycycline treatment at E12.5
• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5

growth/size
• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
• following doxycycline treatment at E12.5
• following doxycycline treatment at E10.5 the overall shape of the head is more rounded
• shortened face following doxycycline treatment at E10.5


Mouse Genome Informatics
cn33
    Gja1tm1Gfi/Gja1tm1Gfi
Tg(Wnt1-cre)11Rth/0

involves: 129/Sv * C57BL/6J * CBA/J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 3 of 5 mutants exhibit coronary abnormalities that include separate ostia for right septal and myocardial coronary tributaries, accessory coronary artery originating from the non-coronary sinus, or tunneling of the left coronary artery through the wall of the aorta, however do not exhibit outflow tract defects


Mouse Genome Informatics
cn34
    Pbx1tm1Koss/Pbx1tm1Koss
Pbx2tm1Mlc/Pbx2+
Tg(Wnt1-cre)11Rth/0

involves: 129P2/OlaHsd * 129S/Sv * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

craniofacial

nervous system
N
• cranial neural crest cell migration and olfactory placodes are normal (J:178316)

digestive/alimentary system

growth/size


Mouse Genome Informatics
cn35
    Nrg1tm4Cbm/Nrg1tm4.1Cbm
Tg(Wnt1-cre)11Rth/0

involves: 129P2/OlaHsd * BALB/cJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• mice exhibit normal myelination (J:199150)
• small diameter and few intrafusal fibers

behavior/neurological
• on an inverted grid, mice loss their grip 5 times faster than control mice
• impaired left/right coordination with frequent hopping

muscle
• small diameter and few intrafusal fibers


Mouse Genome Informatics
cn36
    Gja1tm1Kwi/Gja1tm1Kwi
Tg(Wnt1-cre)11Rth/0

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• normal embryonic development and cardiac morphogenesis is observed


Mouse Genome Informatics
cn37
    Pkd1tm3Jzh/Pkd1tm3Jzh
Tg(Wnt1-cre)11Rth/?

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• the sphenoid bones are much smaller
• early postnatal obliteration of the presphenoid synchondrosis results in the shortening of the presphenoid bone
• the growth of the upper jaw is profoundly retarded where the nasal, premaxillary and maxillary bones are severely reduced in length by three weeks of age
• mineralization of the caudal nasal bone is markedly reduced
• noticeable by three weeks after birth
• maxilla hypoplasia leads to an abnormal apposition of the incisors (class III malocclusion)
• shortened and bent snouts are obvious three weeks after birth resulting from abnormal nasal bone growth in the rostral direction

skeleton
• the sphenoid bones are much smaller
• early postnatal obliteration of the presphenoid synchondrosis results in the shortening of the presphenoid bone
• the growth of the upper jaw is profoundly retarded where the nasal, premaxillary and maxillary bones are severely reduced in length by three weeks of age
• mineralization of the caudal nasal bone is markedly reduced
• noticeable by three weeks after birth
• maxilla hypoplasia leads to an abnormal apposition of the incisors (class III malocclusion)
• early postnatal obliteration of the presphenoid synchondrosis results in the shortening of the sphenoid bones
• there is a population of apoptotic cells in the perichondrium of the presphenoid synchondrosis prior to its closure
• synchondrosal chondrocytes have reduced proliferative activity
• there is a population of apoptotic cells in the perichondrium of the presphenoid synchondrosis prior to its closure
• there is a delay in the intramembranous ossification of the facial and calvarial bones noted at 5 days after birth

growth/size
• shortened and bent snouts are obvious three weeks after birth resulting from abnormal nasal bone growth in the rostral direction


Mouse Genome Informatics
cn38
    Mkl2Gt(RRJ478)Byg/Mkl2Gt(RRJ478)Byg
Tg(Wnt1-cre)11Rth/0

involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected numbers of newborns are seen (11.5% instead of the expected 25%), indicating partial lethality, however lethality is lower than in single Mkl2 homozygotes


Mouse Genome Informatics
cn39
    Gt(ROSA)26Sortm2(DTA)Riet/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• numerous anomalies are evident in the branching pattern of the facial nerve


Mouse Genome Informatics
cn40
    Dvl3tm1Awb/Dvl3tm1Awb
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129S/Sv * Black Swiss * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• at E10.5, E14.5 and E18.5, cardiac neural crest cell development is normal (J:142392)


Mouse Genome Informatics
cn41
    Plxnd1tm1.1Tmj/Plxnd1tm1.1Tmj
Tg(Wnt1-cre)11Rth/0

involves: 129S/SvEv * 129S4/SvJaeSor * C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• normal numbers of mice are born (J:143763)

cardiovascular system
N
• mice exhibit normal cardiac development with normal outflow tract septation (J:143763)


Mouse Genome Informatics
cn42
    Plxnd1tm1Ddg/Plxnd1tm1.1Tmj
Tg(Wnt1-cre)11Rth/0

involves: 129S/SvEv * C57BL/6 * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit a 3-fold increase in the number of proprioceptive synaptic contacts with identified cutaneous maximus motor neurons compared to in wild-type mice
• 43% of cutaneous motor neurons receive monosynaptic input after stimulation of cutaneous maximus afferents unlike wild-type motor neurons
• however, monosynaptic specificity from the tricep is normal

behavior/neurological
N
• mice exhibit no behavior deficits (J:149553)


Mouse Genome Informatics
cn43
    Sox9tm2Crm/Sox9tm2Crm
Tg(Wnt1-cre)11Rth/0

involves: 129S/SvEv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Skeletal image of newborn Sox9tm2Crm/Sox9tm2Crm Tg(Wnt1-cre)11Rth/0 mice

mortality/aging
• die in the immediate postnatal period from respiratory distress

respiratory system
• absent thyroid cartilage

craniofacial
• the body of the hyoid is missing
• the lesser horns are missing
• all elements derived from the second and third branchial arches are missing
• large cleft secondary palate

skeleton
• the body of the hyoid is missing
• the lesser horns are missing
• absent thyroid cartilage
• no discernible chondrogenic mesenchyme condensations are seen at E13.5
• all cartilages and endochondral bones in the prechordal region are missing at E18.5
• endochondrial bone formation derived from cranial neural crest cells is missing, however cranial neural crest cells appear to migrate normally to their target locations

digestive/alimentary system
• large cleft secondary palate

hearing/vestibular/ear

growth/size
• large cleft secondary palate


Mouse Genome Informatics
cn44
    Sox9tm2Crm/Sox9+
Tg(Wnt1-cre)11Rth/0

involves: 129S/SvEv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• mildly hypoplastic craniofacial skeleton
• small cleft secondary palate

digestive/alimentary system
• small cleft secondary palate

growth/size
• small cleft secondary palate


Mouse Genome Informatics
cn45
    Wlstm1.1Lan/Wlstm1.1Lan
Tg(Wnt1-cre)11Rth/0

involves: 129S/SvEv * C57BL/6J * CBA/J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

embryogenesis
• mutant mice exhibit a shortened anteroposterior axis
• mutant phenotype is obvious as early as E9.5 due to the presence of a shortened neural tube

nervous system
• mutant phenotype is obvious as early as E9.5 due to the presence of a shortened neural tube
• mutant mice exhibit no apparent isthmus
• at E12.5 a severely truncated forebrain
• absent midbrain
• at E10.5 verified deletion of regions of the metencephalon
• at E12.5


Mouse Genome Informatics
cn46
    Fgf15tm1Sms/Fgf15tm1Sms
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• at E12.5, homozygotes exhibit successful septation of the distal outflow tract; however, the number of NCCs contributing to the proximal outflow tract is significantly reduced
• at E9.5, cardiac NCCs migrate to the developing caudal pharyngeal arches of mutant embryos in numbers comparable to those of wild-type embryos; however, at E11.5, NCCs fail to invaginate on the right side of the proximal aortic sac at the level of its connection with the 6th aortic arch arteries
• as a result, the conotruncal cushions remain oriented laterally relative to one another

cardiovascular system
• at E12.5, homozygotes exhibit successful septation of the distal outflow tract; however, the number of NCCs contributing to the proximal outflow tract is significantly reduced
• homozygotes exhibit abnormal NCC behavior during outflow tract remodeling

nervous system
• at E12.5, homozygotes exhibit successful septation of the distal outflow tract; however, the number of NCCs contributing to the proximal outflow tract is significantly reduced

cellular
• at E9.5, cardiac NCCs migrate to the developing caudal pharyngeal arches of mutant embryos in numbers comparable to those of wild-type embryos; however, at E11.5, NCCs fail to invaginate on the right side of the proximal aortic sac at the level of its connection with the 6th aortic arch arteries
• as a result, the conotruncal cushions remain oriented laterally relative to one another


Mouse Genome Informatics
cn47
    Pitx2tm1.1Sac/Pitx2tm2Sac
Tg(Wnt1-cre)11Rth/?
Gt(ROSA)26Sortm1Sor/?

involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• devoid of pigment except for a cone shaped region in the anterior segment
• retinal pigment layer is normal at E10.5 but pigment loss begins at E12.5
• corneal stroma and epithelium are absent
• hypomorphic hyaloid blood vessels
• muscle bundles present adjacent to the anterior segment
• eye stalk fails to extend at E12.5
• eyes directly attached to ventral diencephalon by E14.5
• retinal ganglion cell axons enter ventral thalamus and form an optic chiasma-like structure
• eyes are not visible externally at E16.5
• eyes present but buried within the skull near the midline directly beneath the brain
• lens and retina present

pigmentation
• devoid of pigment except for a cone shaped region in the anterior segment
• retinal pigment layer is normal at E10.5 but pigment loss begins at E12.5

nervous system

muscle
• muscle bundles present adjacent to the anterior segment


Mouse Genome Informatics
cn48
    Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
HhatTg(TFAP2A-cre)1Will/HhatTg(TFAP2A-cre)1Will
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• hypoplastic, particularly the trigeminal ganglion
• maxillary branch is consistently narrower than in controls


Mouse Genome Informatics
cn49
    Ctnnb1tm2Kem/Ctnnb1tm2.1Kem
Gt(ROSA)26Sortm1(Ctnnb1)Kem/Gt(ROSA)26Sortm1(Ctnnb1)Kem
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die within hours of birth probably because of an inability to feed


Mouse Genome Informatics
cn50
    Ctnnb1tm2Kem/Ctnnb1tm2.1Kem
Gt(ROSA)26Sortm1(Ctnnb1)Kem/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

nervous system
• brain defects

craniofacial
• impaired morphogenesis of craniofacial structures


Mouse Genome Informatics
cn51
    Hand2tm1Cse/Hand2tm1Cse
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
N
• palate is normal (J:149232)
• no changes in cell proliferation or apoptosis are observed in palatal shelves at E13.5 (J:149232)


Mouse Genome Informatics
cn52
    Hand2tm1Cse/Hand2tm1Dsr
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryos begin to die by 12 dpc and no live embryos are recovered at 13 dpc

cardiovascular system
• blood pools in major vessels, heart, liver, and coelom by 12 dpc
• circulatory defects develop by 12 dpc

homeostasis/metabolism
• number of neuronal cells in sympathetic nervous system expressing tyrosine hydroxylase or dopamine beta-hydroxylase is greatly reduced compared to controls at 12.5 dpc

nervous system
N
• neural crest cell colonization of the sympathetic nervous system is normal, and sympathetic nervous system differentiation is unaffected in mutant embryos (J:122604)
• catecholaminergic differentiation of the sympathetic nervous system is abnormal in mutants; fewer neurons produce enzymes needed for synthesis of noradrenaline than in wild-type controls


Mouse Genome Informatics
cn53
    Tgfbr2tm1Karl/Tgfbr2tm1Karl
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

craniofacial
• malformations of cranial bones at E18

cardiovascular system
• abnormal branching of the left carotid artery from the brachiocephalic trunk in mutant mice
• venous congestion
• defective separation of the aorta from the pulmonary trunk, leading to persistent truncus arteriosis
• exhibit vasodilatation of the jugular veins
• heart defects lead to functional right-sided heart failure with venous congestion, resulting in a vasodilatation of the jugular veins

endocrine/exocrine glands
• 2 of 5 do not have parathyroid glands
• 3 of 5 exhibit hypoplastic parathyroid glands at E18
• thymus gland is 58% the size of wild-type at E18

immune system
• thymus gland is 58% the size of wild-type at E18

nervous system
• defect in neural crest cell differentiation in the pharyngeal apparatus but not in the migration or survival of neural crest cells
• absence of neural crest-derived smooth muscle cells
• midbrain abnormalities
• hindbrain abnormalities

skeleton
• malformations of cranial bones at E18
• malformation of cartilage at E18

hematopoietic system
• thymus gland is 58% the size of wild-type at E18

digestive/alimentary system

embryogenesis
• defect in neural crest cell differentiation in the pharyngeal apparatus but not in the migration or survival of neural crest cells
• absence of neural crest-derived smooth muscle cells

muscle
• exhibit vasodilatation of the jugular veins

growth/size

Mouse Models of Human Disease
OMIM IDRef(s)
DiGeorge Syndrome; DGS 188400 J:96359


Mouse Genome Informatics
cn54
    Gata6tm2Msp/Gata6tm2Msp
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between E18.5 and P1

cardiovascular system
• exhibit a spectrum of aortic arch patterning and cardiac outflow tract septation defects indistinguishable from those seen in mice homozygous for Gata6tm2Msp and hemizygous for Tg(Tagln-cre)1Jjl
• hypoplastic aortic arch
• seen as early as E9.5
• membranous ventricular septal defect


Mouse Genome Informatics
cn55
    Acvr1tm1Vk/Acvr1tm1.1Vk
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants that are born alive die during the first postnatal day
• about 40% die in utero (J:90453)
• only 60% of expected numbers are recovered at birth, however the expected numbers are recovered at E14, indicating 40% lethality between E14 and birth (J:90988)

cardiovascular system
• display abnormal regression of the pharyngeal arch arteries
• at E11.5, the 6th arteries display bilaterally inappropriate regression
• at E11.5, the 3rd arteries display bilaterally inappropriate regression
• aortic arch defects
• 77% exhibit either a short or missing brachiocephalic artery so that the right common carotid artery directly branches from the truncus arteriosus
• 77% exhibit either a short or missing brachiocephalic artery
• the distal outflow tract has reduced numbers of neural crest cells
• the proximal outflow tract is essentially devoid of neural crest cells
• differentiation of neural crest cells to smooth muscle around aortic arch arteries is deficient
• the proximal outflow tract is essentially devoid of neural crest cells while the distal outflow tract has reduced numbers of neural crest cells
• outflow tract cushions are reduced in size
• 100% penentrance or persistent truncus arteriosus type A2 (complete failure of outflow tract septation)
• persistent truncus arteriosus is associated with a ventricular septation defect
• 100% penetrance
• 85% show hyperplastic right ventricle

nervous system
• the distal outflow tract has reduced numbers of neural crest cells
• the proximal outflow tract is essentially devoid of neural crest cells
• differentiation of neural crest cells to smooth muscle around aortic arch arteries is deficient

craniofacial
• display abnormal regression of the pharyngeal arch arteries
• at E11.5, the 6th arteries display bilaterally inappropriate regression
• at E11.5, the 3rd arteries display bilaterally inappropriate regression
• squamous parts of the frontal bones lack ossification towards the metopic region, resulting in enlarged frontal fontanels in newborns
• squamal bones lack the retrotympanic process
• the temporal squama is smaller, lacking the lower portion with the mandibular fossa and its joint cartilage
• zygomatic arches are incomplete in newborns, with developed maxillary zygomatic process but completely absent jugal (zygomatic) bone and zygomatic process of the squamal bone
• coronoid process of the mandible is rudimentary in size
• the mental symphysis is not formed resulting in persistently separate mandibular bones
• hypotrophic mandible is apparent as early as E14
• mandible is about 40% shorter
• completely absent jugal (zygomatic) bone
• slightly shorter manubrium mallei
• the anterior cartilage derived from the distal extremity of Meckel's cartilage is absent
• anterior region of Meckel's cartilage displays retarded growth and also fails to fuse at E15
• display approximately a 3-fold reduction in proliferation of chondrocytes in the anterior and interior parts of Meckel's cartilage at E13
• complete cleft of the secondary palate
• palatal shelves fail to elevate, either bilaterally or unilaterally, at E14
• in newborns, the unfused palatal shelves are bilaterally elevated, indicating that cleft palate develops as a result of delayed, asynchronous elevation of palatal shelves
• newborns have a shorter head

embryogenesis
• display abnormal regression of the pharyngeal arch arteries
• at E11.5, the 6th arteries display bilaterally inappropriate regression
• at E11.5, the 3rd arteries display bilaterally inappropriate regression
• the distal outflow tract has reduced numbers of neural crest cells
• the proximal outflow tract is essentially devoid of neural crest cells
• differentiation of neural crest cells to smooth muscle around aortic arch arteries is deficient
• migration of mutant neural crest cells to the outflow tract is impaired

behavior/neurological
• newborns lack milk in stomachs and fail to suckle

digestive/alimentary system
• complete cleft of the secondary palate
• palatal shelves fail to elevate, either bilaterally or unilaterally, at E14
• in newborns, the unfused palatal shelves are bilaterally elevated, indicating that cleft palate develops as a result of delayed, asynchronous elevation of palatal shelves

hearing/vestibular/ear
• slightly shorter manubrium mallei

skeleton
• squamous parts of the frontal bones lack ossification towards the metopic region, resulting in enlarged frontal fontanels in newborns
• squamal bones lack the retrotympanic process
• the temporal squama is smaller, lacking the lower portion with the mandibular fossa and its joint cartilage
• zygomatic arches are incomplete in newborns, with developed maxillary zygomatic process but completely absent jugal (zygomatic) bone and zygomatic process of the squamal bone
• coronoid process of the mandible is rudimentary in size
• the mental symphysis is not formed resulting in persistently separate mandibular bones
• hypotrophic mandible is apparent as early as E14
• mandible is about 40% shorter
• completely absent jugal (zygomatic) bone
• slightly shorter manubrium mallei
• secondary cartilage of the mandibular condyle does not develop, making the temporomandibular articulation undetectable
• the secondary cartilage of the mandibular angular process is completely missing
• the anterior cartilage derived from the distal extremity of Meckel's cartilage is absent
• anterior region of Meckel's cartilage displays retarded growth and also fails to fuse at E15
• display approximately a 3-fold reduction in proliferation of chondrocytes in the anterior and interior parts of Meckel's cartilage at E13

cellular
• differentiation of neural crest cells to smooth muscle around aortic arch arteries is deficient
• migration of mutant neural crest cells to the outflow tract is impaired

growth/size
• complete cleft of the secondary palate
• palatal shelves fail to elevate, either bilaterally or unilaterally, at E14
• in newborns, the unfused palatal shelves are bilaterally elevated, indicating that cleft palate develops as a result of delayed, asynchronous elevation of palatal shelves
• newborns have a shorter head


Mouse Genome Informatics
cn56
    Fgfr1tm1Jpa/Fgfr1tm1Jpa
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

nervous system
• dorsal cerebellum development is abnormal
• inferior colliculus is deleted in the posterior midbrain
• the vermis is present but severely malformed


Mouse Genome Informatics
cn57
    Nf1tm1Par/Nf1tm1Par
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size

respiratory system
• pups do not initiate normal respiration

nervous system
• increase in the number of adrenal medullary cells, suggesting pheochromocytoma
• massively enlarged sympathetic ganglia that consist of axons that stain for neurofilament and small cell bodies with large nuclei that express tyrosine hydroxylase, a morphology consistent with ganglioneuroma or ganglioneurosarcoma

endocrine/exocrine glands
• a thinning and distortion of the adrenal cortex
• increase in the number of adrenal medullary cells, suggesting pheochromocytoma

tumorigenesis
• develop tumors of neural crest origin such as ganglioneuroma, ganglioneurosarcoma, and pheochromocytoma

cardiovascular system
N
• normal cardiac development (J:80323)

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:80323


Mouse Genome Informatics
cn58
    Pygo2tm1.1Ssp/Pygo2tm1.2Ssp
Tg(Wnt1-cre)11Rth/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• at E12.5, lens size is reduced comparable to Pygo2tm1Lan/Pygo2tm1.1Lan mice


Mouse Genome Informatics
cn59
    Gt(ROSA)26Sortm2(Pax3)Joe/Gt(ROSA)26Sortm2(Pax3)Joe
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• authors state that mice exhibit identical phenotypes as observed in Gt(ROSA)26Sortm2Joe/Gt(ROSA)26Sortm2Joe Pax3tm1(cre)Joe/Pax3+ mice
• authors state that mice exhibit identical phenotypes as observed in Gt(ROSA)26Sortm2Joe/Gt(ROSA)26Sortm2Joe Pax3tm1(cre)Joe/Pax3+ mice

vision/eye
• authors state that mice exhibit identical phenotypes as observed in Gt(ROSA)26Sortm2Joe/Gt(ROSA)26Sortm2Joe Pax3tm1(cre)Joe/Pax3+ mice

digestive/alimentary system
• authors state that mice exhibit identical phenotypes as observed in Gt(ROSA)26Sortm2Joe/Gt(ROSA)26Sortm2Joe Pax3tm1(cre)Joe/Pax3+ mice

growth/size
• authors state that mice exhibit identical phenotypes as observed in Gt(ROSA)26Sortm2Joe/Gt(ROSA)26Sortm2Joe Pax3tm1(cre)Joe/Pax3+ mice


Mouse Genome Informatics
cn60
    Gt(ROSA)26Sortm2(Pax3)Joe/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• in one mouse

digestive/alimentary system
• in one mouse

growth/size
• in one mouse


Mouse Genome Informatics
cn61
    Pygo2tm1.1Ssp/Pygo2tm1.2Ssp
Tg(Pax6-cre,GFP)1Pgr/?
Tg(Wnt1-cre)11Rth/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• at E12.5, lens reduction is more severe that in either single cre cross but not as severe as in the Pygo2 null homozygotes


Mouse Genome Informatics
cn62
    Fgfr1tm2Jrt/Fgfr1tm2Jrt
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
N
• the palate is closed, unlike in mice homozygous for Fgfr1tm2Jrt alone (J:81179)
• posterior part are always affected
• posterior part are always affected
• reduced gonial bone
• variable deficiencies
• variable deficiencies
• disruption in second branchial arch development is similar to that in Fgfr1tm2Jrt homozygotes

hearing/vestibular/ear
• reduced gonial bone
• variable deficiencies
• variable deficiencies

skeleton
• posterior part are always affected
• posterior part are always affected
• reduced gonial bone
• variable deficiencies
• variable deficiencies

embryogenesis
• disruption in second branchial arch development is similar to that in Fgfr1tm2Jrt homozygotes


Mouse Genome Informatics
cn63
    Fgfr1tm1Jpa/Fgfr1tm1Jpa
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
N
• at E9.5, no defects are seen in the early development of the second branchial arch unlike mice homozygous for Fgfr1tm2Jrt (J:81179)
• also, the malleus, incus, stapes, styloid process, tympanic ring, alisphenoid and squamosum are normal (J:81179)
• lesser horn points laterally
• in newborns

digestive/alimentary system
• in newborns

skeleton
• lesser horn points laterally

growth/size
• in newborns


Mouse Genome Informatics
cn64
    Fgfr1tm1Jpa/Fgfr1tm1.1Jpa
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
N
• at E9.5, no defects are seen in the early development of the second branchial arch unlike mice homozygous for Fgfr1tm2Jrt (J:81179)
• no enhancement in later craniofacial phenotypes relative to mice homozygous for Fgfr1tm1Jrt that carry the Tg(Wnt1-cre)11Rth transgene

digestive/alimentary system

skeleton
• no enhancement in later craniofacial phenotypes relative to mice homozygous for Fgfr1tm1Jrt that carry the Tg(Wnt1-cre)11Rth transgene

growth/size


Mouse Genome Informatics
cn65
    Ednrbtm1Nrd/Ednrbtm1Nrd
Gt(ROSA)26Sortm1(EYFP)Cos/Gt(ROSA)26Sor+
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die 5 weeks after birth

growth/size

digestive/alimentary system

pigmentation
• mice lack coat pigment in the trunk

embryogenesis
• enteric neural crest cells fail to reach the anus

integument
• mice lack coat pigment in the trunk

cellular
• enteric neural crest cells fail to reach the anus


Mouse Genome Informatics
cn66
    Pax3tm2Joe/Pax3tm2Joe
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant die immediately after birth

growth/size
• smaller than wild-type littermates at birth

homeostasis/metabolism
• cyanotic at birth

muscle
• poorly developed limb and diaphragm musculature at birth
• skeletal muscle is severely deficient in the limbs
• severe deficiency of forelimb musculature

respiratory system
• newborns fail to initiate respirations

embryogenesis
• occasional mild spina bifida are seen at birth

cardiovascular system
N
• normal septation of the aorta and pulmonary artery (J:159124)

nervous system
• occasional mild spina bifida are seen at birth


Mouse Genome Informatics
cn67
    Kif3atm2Gsn/Kif3atm2Gsn
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• increased neural crest cell proliferation in the facial prominences, as shown by BrdU immunostaining
• cranial neural crest cells do not extend primary cilia
• primary cilia are truncated in frontonasal prominence

nervous system
• cranial neural crest cells do not extend primary cilia
• primary cilia are truncated in frontonasal prominence
• failure of neural fibers to span the midline

craniofacial
• craniofacial skeleton elements are displaced laterally but their maturation is unaffected
• severely dysmorphic
• anterior cranium occultum
• trabecular basal plate is reduced to bony nodules or absent at E17.5
• is reduced to bony nodules or absent at E17.5
• laterally displaced and underdeveloped resulting in an abnormal opening in the skull
• 30% shorter than wild-type
• laterally displaced at E17.5
• laterally displaced at E17.5
• laterally displaced at E17.5
• the palatine bones are dysmorphic and do not extend towards the midline
• some small ectopic ossifications are found in the midline which may or may not be fragments of the palatine bones
• at E11.5 and E12.5 infra-nasal measurements show an increase in frontonasal width
• at E14.5, almost 100% wider than wild-type and at E17.5 120% wider than wild-type
• at E12.5, septum is evident as a bifid condensation and by E16.5 a duplicated nasal septum is present

digestive/alimentary system

skeleton
• craniofacial skeleton elements are displaced laterally but their maturation is unaffected
• severely dysmorphic
• anterior cranium occultum
• trabecular basal plate is reduced to bony nodules or absent at E17.5
• is reduced to bony nodules or absent at E17.5
• laterally displaced and underdeveloped resulting in an abnormal opening in the skull
• 30% shorter than wild-type
• laterally displaced at E17.5
• laterally displaced at E17.5
• laterally displaced at E17.5
• the palatine bones are dysmorphic and do not extend towards the midline
• some small ectopic ossifications are found in the midline which may or may not be fragments of the palatine bones

respiratory system
• at E12.5, septum is evident as a bifid condensation and by E16.5 a duplicated nasal septum is present

vision/eye

cellular
• increased neural crest cell proliferation in the facial prominences, as shown by BrdU immunostaining

growth/size
• at E12.5, septum is evident as a bifid condensation and by E16.5 a duplicated nasal septum is present


Mouse Genome Informatics
cn68
    Ndst1tm1Grob/Ndst1tm1Grob
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
N
• lacrimal gland development is normal (J:130571)


Mouse Genome Informatics
cn69
    Ndst1tm1Grob/Ndst1tm1Grob
Ndst2tm1Lkj/Ndst2tm1Lkj
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• disruption of lacrimal gland budding

endocrine/exocrine glands
• disruption of lacrimal gland budding


Mouse Genome Informatics
cn70
    Snai1tm1Grid/Snai1tm2Grid
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• animals are viable, fertile, and exhibit no phenotypic abnormalities


Mouse Genome Informatics
cn71
    Snai1tm1Grid/Snai1tm2Grid
Snai2tm2Grid/Snai2tm2Grid
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• resulting from cleft palate

craniofacial
• enlarged in neonates
• nenates have shortened parietal bones
• mandible is shorter than in wild-type
• in neonates
• anterior palatal shelves of some double null mutants show subtle size and shape differences relative to wild-type palates at E13.5 and 14.5
• neonates show cleft palate
• palatal shelves remain in a vertical growth orientation and fail to elevate

skeleton
• enlarged in neonates
• nenates have shortened parietal bones
• mandible is shorter than in wild-type
• in neonates

digestive/alimentary system
• anterior palatal shelves of some double null mutants show subtle size and shape differences relative to wild-type palates at E13.5 and 14.5
• neonates show cleft palate
• palatal shelves remain in a vertical growth orientation and fail to elevate

growth/size
• anterior palatal shelves of some double null mutants show subtle size and shape differences relative to wild-type palates at E13.5 and 14.5
• neonates show cleft palate
• palatal shelves remain in a vertical growth orientation and fail to elevate


Mouse Genome Informatics
cn72
    Tg(Wnt1-cre)11Rth/0
Zfpm2tm1Sho/Zfpm2tm2Sho

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice survive normally (J:150452)

cardiovascular system
N
• no detectable defects in heart morphogenesis or coronary development are detected (J:150452)


Mouse Genome Informatics
cn73
    Jag1tm2Grid/Jag1tm2Grid
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• maxilla deficiencies lead to poor feeding and death around one month of age

growth/size
• the palatal dimensions are proportionally smaller, however the structural components are in tact
• mutants exhibit reduced proliferation in the palate shelves at E14.5 and in the adjacent palatal epithelium
• mutants exhibit reduced hyaluronic acid in the palate shelves at E14.5
• mutants exhibit aberrant vascular pattering in the palate including reduced vascular branching at E14.5 and E15.5
• at E14.5, palatal shelf elevation above the tongue occurs normally but palatal elongation is reduced anteriorly, whereas the posterior palate shelf length is unaffected
• mutants exhibit delayed palatal shelf elongation
• some E15.5 mutants show delayed palate shelf apposition and the persistence of the epithelial seam, however palate fusion occurs in all mutants
• palate shelf height is reduced in both the anterior and posterior regions
• midfacial hypoplasia resulting in a reduction in anterior facial width

craniofacial
• shortened maxillary regions; anterior-posterior facial length is normal at P0 but over time the mutants exhibit smaller maxillary lengths
• the inframaxillary length and the posterior-anterior length are reduced
• dental occlusion is misaligned with severe midface hypoplasia requiring trimming of the lower incisors weekly
• the palatal dimensions are proportionally smaller, however the structural components are in tact
• mutants exhibit reduced proliferation in the palate shelves at E14.5 and in the adjacent palatal epithelium
• mutants exhibit reduced hyaluronic acid in the palate shelves at E14.5
• mutants exhibit aberrant vascular pattering in the palate including reduced vascular branching at E14.5 and E15.5
• at E14.5, palatal shelf elevation above the tongue occurs normally but palatal elongation is reduced anteriorly, whereas the posterior palate shelf length is unaffected
• mutants exhibit delayed palatal shelf elongation
• some E15.5 mutants show delayed palate shelf apposition and the persistence of the epithelial seam, however palate fusion occurs in all mutants
• palate shelf height is reduced in both the anterior and posterior regions
• midfacial hypoplasia resulting in a reduction in anterior facial width

skeleton
• shortened maxillary regions; anterior-posterior facial length is normal at P0 but over time the mutants exhibit smaller maxillary lengths
• the inframaxillary length and the posterior-anterior length are reduced
• dental occlusion is misaligned with severe midface hypoplasia requiring trimming of the lower incisors weekly

behavior/neurological
• mutants exhibit poor feeding after 30 days of age due to malocclusion and require soft mouse chow

cardiovascular system
• mutants exhibit aberrant vascular pattering in the palate; reduced vascular branching in the palate at E14.5 and E15.5, reduced vasculature organization and vessel size, poor vascular smooth muscle investment, and irregular vessel formation

digestive/alimentary system
• the palatal dimensions are proportionally smaller, however the structural components are in tact
• mutants exhibit reduced proliferation in the palate shelves at E14.5 and in the adjacent palatal epithelium
• mutants exhibit reduced hyaluronic acid in the palate shelves at E14.5
• mutants exhibit aberrant vascular pattering in the palate including reduced vascular branching at E14.5 and E15.5
• at E14.5, palatal shelf elevation above the tongue occurs normally but palatal elongation is reduced anteriorly, whereas the posterior palate shelf length is unaffected
• mutants exhibit delayed palatal shelf elongation
• some E15.5 mutants show delayed palate shelf apposition and the persistence of the epithelial seam, however palate fusion occurs in all mutants
• palate shelf height is reduced in both the anterior and posterior regions

Mouse Models of Human Disease
OMIM IDRef(s)
Alagille Syndrome 1; ALGS1 118450 J:181120


Mouse Genome Informatics
cn74
    Hand2tm1Cse/Hand2+
Tg(Wnt1-cre)11Rth/0

involves: 129S1/Sv * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no viable embryos are found at 15.5 dpc, with death prior to complete development of the cardiovascular system
• when pregnant mothers are treated with isoproterenol, approximately half of the mutant embryos survive to 15.5 dpc with about the same number surviving to birth

embryogenesis
N
• neural crest cell migration and smooth muscle differentiation are unaffected (J:155265)

cardiovascular system
• pulmonary stenosis is observed at 16.5 dpc (in 37.5% of mutants)
• embryos show abnormal origin of the right subclavian artery including retroesophageal right subclavian artery at 16.5 dpc (in 100% of mutants)
• observed at 16.5 dpc (in 87.5% of mutants)
• observed at 16.5 dpc (in 62.5% of mutants)
• hypertrabeculation in the right ventricle is observed at 17.5 dpc due to decrease in number of cells exiting the cell cycle
• embyos display membranous ventricular defects at 16.5 dpc (in 100% of mutants)
• size of right ventricle is increased in embryos at 17.5 dpc
• proliferation is increased 2-fold over controls in trabecular zone of the right ventricle at 13.5 and 15.5 dpc with no increase observed in the compact zone of the heart or the trabecular zone of the left ventricle

muscle
• hypertrabeculation in the right ventricle is observed at 17.5 dpc due to decrease in number of cells exiting the cell cycle
• proliferation is increased 2-fold over controls in trabecular zone of the right ventricle at 13.5 and 15.5 dpc with no increase observed in the compact zone of the heart or the trabecular zone of the left ventricle

cellular
• proliferation is increased 2-fold over controls in trabecular zone of the right ventricle at 13.5 and 15.5 dpc with no increase observed in the compact zone of the heart or the trabecular zone of the left ventricle
• doubling in proportion of cycling cardiomyocytes is detected in trabecular zone of right ventricle

hematopoietic system
• the thymus is located lateral to the aortic arch arteries in a more rostral position compared to the normal location on the ventral side of the outflow tract close to the heart

immune system
• the thymus is located lateral to the aortic arch arteries in a more rostral position compared to the normal location on the ventral side of the outflow tract close to the heart

endocrine/exocrine glands
• the thymus is located lateral to the aortic arch arteries in a more rostral position compared to the normal location on the ventral side of the outflow tract close to the heart


Mouse Genome Informatics
cn75
    Hand2tm1.1Majh/Hand2tm1.1Majh
Tg(Wnt1-cre)11Rth/0

involves: 129S1/SvImJ * C57BL/6 * CBA * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryos die around E12
• treatment of dams with a mixture of catecholamine intermediates allows mice to survive to birth

nervous system
N
• despite loss of Hand2 expression in neural crest cells, neural crest migration is normal (J:137726)
• significant reduction in the proliferation of neuronal precursor cells and neuroblasts by E12
• patterning defects in the stomach suggest decrease in fiber density and relative disorganization of the plexus
• abnormal patterning of ganglia and decrease in ganglia depth in the stomach at E14
• at E16 decrease in fiber and ganglia density at the oral end of the stomach
• density increases from the oral to the anal end but remains lower than in stomachs of control embryos
• marked increase in cell size and decrease in cell density in the stomach at E14
• at E16 decrease in fiber and ganglia density at the oral end of the stomach
• density increases from the oral to the anal end but remains lower than in stomachs of control embryos
• at E12 there is a reduction in the number of cells expressing either a pan-neuronal marker (Hu) and catecholaminergic marker (TH) as well as a decrease in the proportion of cells expressing both markers
• the proportion of neurons and expression of TH continues to decrease with age
• at P0 only a few scattered cells remain that express TH and the sympathetic chain is absent

cardiovascular system
• in catecholamine rescued embryos at E14

craniofacial
• in catecholamine rescued embryos at E14
• in catecholamine rescued embryos at E14

embryogenesis
• in catecholamine rescued embryos at E14

skeleton
• in catecholamine rescued embryos at E14
• in catecholamine rescued embryos at E14

growth/size
• in catecholamine rescued embryos at E14

cellular
• significant reduction in the proliferation of neuronal precursor cells and neuroblasts by E12


Mouse Genome Informatics
cn76
    Nfatc1tm1Glm/Nfatc1tm1Glm
Tg(Wnt1-cre)11Rth/0
Gt(ROSA)26Sortm1Sho/Gt(ROSA)26Sor+

involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• thinning of neural crest-derived mesenchyme in the distal outflow tract (dOFT) of E12.5 embryos, affecting the formation of the base of the aortic valve


Mouse Genome Informatics
cn77
    Bdnftm1Krj/Bdnftm1Lfr
Tg(Wnt1-cre)11Rth/0

involves: 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• at 1 month of age 78% of mutants clutch compared to 8% of wild-type mice and by 6 months all mutants clutch compared to 16% of wild-type
• at 4 - 5 weeks of age performance on the rotarod test is impaired

nervous system
• tyrosine hydroxylase-positive neurons are reduced by about 27% and 23% at postnatal day 0 and 120, respectively and appear disorganized
• the extent of the substantia nigra pars compacta appears reduced in coronal sections but the density of calbindin-positive neurons appears increased


Mouse Genome Informatics
cn78
    Pax9tm1.1Hpt/Pax9tm1.1Hpt
Tg(Wnt1-cre)11Rth/?

involves: 129S2/SvPas * C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die at birth

craniofacial
• the palatal processes of the maxilla is displaced laterally
• the palatal processes of the palatine is displaced laterally
• tooth development is arrested at the bud stage

behavior/neurological
• mice die with no evidence of feeding

digestive/alimentary system
• the palatal processes of the maxilla is displaced laterally
• the palatal processes of the palatine is displaced laterally

skeleton
• the palatal processes of the maxilla is displaced laterally
• the palatal processes of the palatine is displaced laterally

growth/size
• the palatal processes of the maxilla is displaced laterally