Mouse Genome Informatics
hm1
     Msx1tm1Bero/Msx1tm1Bero
B6.129P2-Msx1tm1Bero
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
complete neonatal lethality ( J:42035 )
• newborn homozygotes die within a few hours after birth
• Background Sensitivity: on a congenic C57BL/6J background, newborn homozygotes die more rapidly than homozygotes on mixed genetic background

craniofacial
abnormal cranium morphology ( J:42035 )
• at birth, homozygotes exhibit a rounded skull
absent alveolar process ( J:42035 )
• newborn homozygotes lack alveolar processes
cleft chin ( J:42035 )
• at ~E13, mandibular development is slightly delayed, resulting in a cleft chin
absent malleus processus brevis ( J:42035 )
• newborn homozygotes lack the short process of the malleus, in the absence of other ear abnormalities
growth retardation of molars ( J:42035 )
• molars develop until E13.5 and reach the bud stage but fail to develop further
abnormal palate morphology ( J:42035 )
• at ~E13, the shape of the secondary palate is slightly altered
cleft secondary palate ( J:42035 , J:104286 )
• all newborn homozygotes show a complete cleft of the secondary palate (J:42035)
absent incisors ( J:42035 )
• newborn homozygotes lack incisors
absent molars ( J:104286 )
• at P0, homozygotes lack mandibular molars
short snout ( J:42035 )
• at birth, homozygotes display a shortened snout
shortened head ( J:42035 )
• at birth, homozygotes display a shortened head

respiratory system
respiratory distress ( J:42035 )
• newborns exhibit gasping respirations prior to death and contain air in their stomachs and intestines
• Background Sensitivity: on a congenic C57BL/6J background, newborn homozygotes contain less air in their stomachs than homozygotes on a mixed genetic background

homeostasis/metabolism
cyanosis ( J:42035 )
• newborn homozygotes become rapidly cyanotic

skeleton
abnormal cranium morphology ( J:42035 )
• at birth, homozygotes exhibit a rounded skull
absent alveolar process ( J:42035 )
• newborn homozygotes lack alveolar processes
cleft chin ( J:42035 )
• at ~E13, mandibular development is slightly delayed, resulting in a cleft chin
absent malleus processus brevis ( J:42035 )
• newborn homozygotes lack the short process of the malleus, in the absence of other ear abnormalities

digestive/alimentary system
abnormal palate morphology ( J:42035 )
• at ~E13, the shape of the secondary palate is slightly altered
cleft secondary palate ( J:42035 , J:104286 )
• all newborn homozygotes show a complete cleft of the secondary palate (J:42035)

hearing/vestibular/ear
absent malleus processus brevis ( J:42035 )
• newborn homozygotes lack the short process of the malleus, in the absence of other ear abnormalities

limbs/digits/tail
limbs/digits/tail phenotype ( J:42035 )
N
• surprisingly, homozygotes exhibit no limb defects (J:42035)

Mouse Models of Human Disease
 OMIM IDRef(s)
Tooth Agenesis, Selective, 1; STHAG1 106600 J:42035


Mouse Genome Informatics
hm2
     Msx1tm1Bero/Msx1tm1Bero
involves: 129P2/OlaHsd
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
nervous system
increased neuron number ( J:99936 )
• at E13.5 homozygotes have significantly more Gnrh1 expressing neurons (1300+/-116) compared to wild-type (939+/-20) and some of these cells are ectopically located in the olfactory epithelium


Mouse Genome Informatics
hm3
     Msx1tm1Bero/Msx1tm1Bero
involves: 129P2/OlaHsd * C57BL/6J
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
nervous system
abnormal roof plate morphology ( J:84975 )
• a normal roof plate fails to form in the caudal diencephalon as indicated by marker analysis
abnormal brain morphology ( J:84975 )
• 1/3 of E11.5 mutants exhibit an indentation at the boundary between the diencephalon and mesencephalon
hydroencephaly ( J:84975 )
• some mutants exhibit hydrocephalus at birth
dilated fourth ventricle ( J:84975 )
• seen in some mutants
abnormal brain commissure morphology ( J:84975 )
• posterior commissure is disorganized at E15.5
abnormal diencephalon morphology ( J:84975 )
• marker analysis indicates that dorsal midline cells are not maintained in prosomere 1 of the diencephalon
• cell death is reduced in the dorsal midline of the diencephalon of E10.5-E12.5 mutants
dilated third ventricle ( J:84975 )
• seen in some mutants

endocrine/exocrine glands
abnormal subcommissural organ morphology ( J:84975 )
• the subcommissural organ is reduced or absent in all mutants at E15.5
• the subcommissural organ is colonized by many nucleated cells instead of mainly neural fibers

embryogenesis
abnormal roof plate morphology ( J:84975 )
• a normal roof plate fails to form in the caudal diencephalon as indicated by marker analysis


Mouse Genome Informatics
ht4
     Msx1tm2.1(cre/ERT2)Bero/Msx1tm1Bero
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
embryogenesis
abnormal embryonic tissue morphology ( J:194129 )
• internal organ development is disrupted due to thoracoabdominoschisis

growth/size
abnormal body wall morphology ( J:194129 )
• at E12.3 embryos show thoracoabdominoschisis (opening of both the thorax and abdomen)

craniofacial
abnormal facial morphology ( J:194129 )
• at E12.5, embryos have highly deformed faces

nervous system
exencephaly ( J:194129 )
• at E12.5

liver/biliary system
abnormal liver development ( J:194129 )
• liver appears rudimentary

vision/eye
abnormal eye morphology ( J:194129 )
• embryos display atrophic eyes at E12.5


Mouse Genome Informatics
cn5
     Msx1tm1Bero/Msx1tm1Bero
Msx2tm1Bero/Msx2tm1Yvla
Taglntm2(cre)Yec/Tagln+
involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac * NMRI
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
cardiovascular system
abnormal artery morphology ( J:173525 )
• superficial temporal artery is more branched than in controls
abnormal carotid artery morphology ( J:173525 )
• at E11.5, carotid artery (CA) overbranching is observed
abnormal vertebral artery morphology ( J:173525 )
• vertebral artery (VA) caliber is increased relative to controls
vascular smooth muscle cell hypoplasia ( J:173525 )
• number of smooth muscle actin-positive cells in CA is half that observed in controls
intracranial aneurysm ( J:173525 )
• in the head, aneurysms are frequently observed
intracranial hemorrhage ( J:173525 )
• in the head, hemorrhages are frequently observed

muscle
vascular smooth muscle cell hypoplasia ( J:173525 )
• number of smooth muscle actin-positive cells in CA is half that observed in controls

nervous system
intracranial hemorrhage ( J:173525 )
• in the head, hemorrhages are frequently observed


Mouse Genome Informatics
cn6
     Msx1tm1Bero/Msx1tm2.1(cre/ERT2)Bero
Msx2tm1Yvla/Msx2tm1Yvla
involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6 * NMRI
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
cardiovascular system
abnormal carotid artery morphology ( J:173525 )
• increased carotid artery vessel diameter is observed
vascular smooth muscle cell hypoplasia ( J:173525 )
• a reduction in vascular smooth muscle cell (VSMC) coverage (depletion of mural cells) is observed

muscle
vascular smooth muscle cell hypoplasia ( J:173525 )
• a reduction in vascular smooth muscle cell (VSMC) coverage (depletion of mural cells) is observed


Mouse Genome Informatics
cx7
     Msx1tm1Bero/Msx1tm1Bero
Msx2tm1Bero/Msx2tm1Bero
involves: 129/Sv * 129P2/OlaHsd * C57BL/6 * C57BL/6J
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
partial embryonic lethality during organogenesis ( J:84975 )
• resorption observed at E10.5 and E11.5, incomplete penetrance

embryogenesis
decreased embryo size ( J:84975 )
• small embryo size at E10.5-E11.5
spina bifida ( J:84975 )
• seen in some embryos

growth/size
decreased embryo size ( J:84975 )
• small embryo size at E10.5-E11.5

nervous system
spina bifida ( J:84975 )
• seen in some embryos
exencephaly ( J:84975 )
• observed in some cases, encompassing the posterior mesencephalon and the rhombencephalon
decreased brain size ( J:84975 )
• small and abnormal brain


Mouse Genome Informatics
cx8
     Msx1tm1Bero/Msx1tm1Bero
Msx2tm1Bero/Msx2tm1Yvla
involves: 129/Sv * BALB/c * C57BL/6 * SJL
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging

craniofacial

digestive/alimentary system


Mouse Genome Informatics
cx9
     Msx1tm1Bero/Msx1tm1Bero
Msx2tm1Bero/Msx2tm1Bero
involves: 129/Sv * C57BL/6 * NMRI
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
complete lethality throughout fetal growth and development ( J:98917 )
• double homozygotes do not survive beyond E15

limbs/digits/tail
abnormal apical ectodermal ridge morphology ( J:98917 )
• maturation of the apical ectodermal ridge is impaired and regression is delayed; however initiation is normal
• at E10.2 and E11.5 the apical ectodermal ridge appears shorter and more diffuse
• at E12.5 the apical ectodermal ridge remains continuos along the entire apex of the limb and appears thicker than normal
small limb buds ( J:98917 )
• limb bud size is reduced by about 1/3 at E10.5 to E11.5 even in somite-matched embryos
• the mesenchymal anterior domain of the limb bud is not maintained after E10.5 and all of the mesenchyme in the limb bud assumes a posterior identity
• in the anterior portion of the limb bud the normal dorsal ventral boundary is not established at E10.5
oligodactyly ( J:98917 )
• at E14.5 about of mutants only have 1 phalange while control embryos have 2
• the missing digit is always the anterior most one
polydactyly ( J:98917 )
• 2 out of 18 mutant forelimbs had 6 digits
interdigital webbing ( J:98917 )
• at E14.5 interdigital webbing is retained
abnormal tarsal bone morphology ( J:98917 )
• the posterior elements are present, the medium elements are severely truncated, and the anterior elements are absent
abnormal carpal bone morphology ( J:98917 )
• the posterior elements are present, the medium elements are severely truncated, and the anterior elements are absent
short limbs ( J:98917 )
• at E14.5 the 3 segments of the limb are about 3/4 of the normal size
• general truncation of the anterior parts of the limbs with systematic loss of the anterior part of the zeugopod

embryogenesis
abnormal apical ectodermal ridge morphology ( J:98917 )
• maturation of the apical ectodermal ridge is impaired and regression is delayed; however initiation is normal
• at E10.2 and E11.5 the apical ectodermal ridge appears shorter and more diffuse
• at E12.5 the apical ectodermal ridge remains continuos along the entire apex of the limb and appears thicker than normal
small limb buds ( J:98917 )
• limb bud size is reduced by about 1/3 at E10.5 to E11.5 even in somite-matched embryos
• the mesenchymal anterior domain of the limb bud is not maintained after E10.5 and all of the mesenchyme in the limb bud assumes a posterior identity
• in the anterior portion of the limb bud the normal dorsal ventral boundary is not established at E10.5

skeleton
abnormal tarsal bone morphology ( J:98917 )
• the posterior elements are present, the medium elements are severely truncated, and the anterior elements are absent
abnormal carpal bone morphology ( J:98917 )
• the posterior elements are present, the medium elements are severely truncated, and the anterior elements are absent
small scapula ( J:98917 )
• at E14.5 the scapula is about 3/4 of the normal size
abnormal pelvic girdle bone morphology ( J:98917 )
• at E14.5 the pelvic girdle is about 3/4 of the normal size
absent pubis ( J:98917 )
• mutants lack the pubis bone corresponding to the anterior part of the pelvis


Mouse Genome Informatics
cx10
     Msx1tm1Bero/Msx1tm1Bero
Msx2tm1Yvla/Msx2tm1Yvla
involves: 129P2/OlaHsd * 129S2/SvPas * BALB/c * C57BL/6 * SJL
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging

craniofacial
abnormal craniofacial morphology ( J:136241 )
• mice exhibit craniofacial malformations

limbs/digits/tail
abnormal limb development ( J:136241 )
• mice exhibit limb malformations

nervous system

growth/size
omphalocele ( J:136241 )
• thoracoabdominoschisis


Mouse Genome Informatics
cx11
     Dlx5tm1Levi/Dlx5tm1Levi
Msx1tm1Bero/Msx1tm1Bero
involves: 129P2/OlaHsd * C57BL/6 * DBA/2
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
mortality/aging
complete neonatal lethality ( J:104286 )
• double homozygotes die soon after delivery

craniofacial
abnormal neurocranium morphology ( J:104286 )
• at P0, double homozygotes exhibit severe retardation of mineralized bone deposition in calvaria
• at P0, double mutant vault bones are smaller and severely perforated with irregular borders relative to those seen in either single homozygote
abnormal basioccipital bone morphology ( J:104286 )
• at P0, double homozygotes display deformed basioccipitals, similar to Dlx5tm1Levi homozygotes
abnormal basisphenoid bone morphology ( J:104286 )
• at P0, double homozygotes display deformed basisphenoids, similar to Dlx5tm1Levi homozygotes
abnormal fontanelle morphology ( J:104286 )
• at P0, double mutant fontanels appear to be open on the midline
abnormal alisphenoid bone morphology ( J:104286 )
• at P0, double homozygotes display a disorganized foramina of the ala temporalis, similar to Dlx5tm1Levi homozygotes
abnormal pterygoid bone morphology ( J:104286 )
• at P0, double homozygotes display deformed pterygoids, similar to Dlx5tm1Levi homozygotes
abnormal squamosal bone morphology ( J:104286 )
• at P0, double homozygotes display deformed squamosal bones, similar to Msx1tm1Bero homozygotes
absent mandibular coronoid process ( J:104286 )
• at P0, double homozygotes lack the coronoid process, similar to single Dlx5tm1Levi homozygotes
micrognathia ( J:104286 )
• at P0, double homozygotes display a shorter and coarser jaw relative to wild-type or to Msx1tm1Bero homozygotes, although not as short as in Dlx5tm1Levi homozygotes
abnormal malleus morphology ( J:104286 )
• at P0, double homozygotes display a malformed malleus with no head, similar to Msx1tm1Bero homozygotes
• in addition, an ectopic bone is present, similar to Dlx5tm1Levi homozygotes
absent malleus head ( J:104286 )
• at P0, double homozygotes display absence of caput mallei
abnormal nasal capsule morphology ( J:104286 )
• at P0, double homozygotes display hypoplasia and asymmetry of the nasal capsules, similar to Dlx5tm1Levi homozygotes
cleft secondary palate ( J:104286 )
• at E13.5, double homozygotes (2/2) display partly formed and elevated shelves which fail to come to contact and fuse
• at P0, double homozygotes (3/3) exhibit a mild clefting, as elevated shelves fail to fuse in the midline, indicating partial rescue of the severe Msx1-related palatal phenotype
absent molars ( J:104286 )
• at P0, double homozygotes lack molar teeth, similar to Msx1tm1Bero homozygotes

digestive/alimentary system
cleft secondary palate ( J:104286 )
• at E13.5, double homozygotes (2/2) display partly formed and elevated shelves which fail to come to contact and fuse
• at P0, double homozygotes (3/3) exhibit a mild clefting, as elevated shelves fail to fuse in the midline, indicating partial rescue of the severe Msx1-related palatal phenotype

skeleton
abnormal neurocranium morphology ( J:104286 )
• at P0, double homozygotes exhibit severe retardation of mineralized bone deposition in calvaria
• at P0, double mutant vault bones are smaller and severely perforated with irregular borders relative to those seen in either single homozygote
abnormal basioccipital bone morphology ( J:104286 )
• at P0, double homozygotes display deformed basioccipitals, similar to Dlx5tm1Levi homozygotes
abnormal basisphenoid bone morphology ( J:104286 )
• at P0, double homozygotes display deformed basisphenoids, similar to Dlx5tm1Levi homozygotes
abnormal fontanelle morphology ( J:104286 )
• at P0, double mutant fontanels appear to be open on the midline
abnormal alisphenoid bone morphology ( J:104286 )
• at P0, double homozygotes display a disorganized foramina of the ala temporalis, similar to Dlx5tm1Levi homozygotes
abnormal pterygoid bone morphology ( J:104286 )
• at P0, double homozygotes display deformed pterygoids, similar to Dlx5tm1Levi homozygotes
abnormal squamosal bone morphology ( J:104286 )
• at P0, double homozygotes display deformed squamosal bones, similar to Msx1tm1Bero homozygotes
absent mandibular coronoid process ( J:104286 )
• at P0, double homozygotes lack the coronoid process, similar to single Dlx5tm1Levi homozygotes
micrognathia ( J:104286 )
• at P0, double homozygotes display a shorter and coarser jaw relative to wild-type or to Msx1tm1Bero homozygotes, although not as short as in Dlx5tm1Levi homozygotes
abnormal malleus morphology ( J:104286 )
• at P0, double homozygotes display a malformed malleus with no head, similar to Msx1tm1Bero homozygotes
• in addition, an ectopic bone is present, similar to Dlx5tm1Levi homozygotes
absent malleus head ( J:104286 )
• at P0, double homozygotes display absence of caput mallei
abnormal nasal capsule morphology ( J:104286 )
• at P0, double homozygotes display hypoplasia and asymmetry of the nasal capsules, similar to Dlx5tm1Levi homozygotes
delayed bone ossification ( J:104286 )
• at P0, double hoomozygotes display delayed fore- and hindlimb ossification and a severe retardation of mineralized bone deposition in calvaria; only slight to mild delays are noted in single homozygotes

hearing/vestibular/ear
abnormal malleus morphology ( J:104286 )
• at P0, double homozygotes display a malformed malleus with no head, similar to Msx1tm1Bero homozygotes
• in addition, an ectopic bone is present, similar to Dlx5tm1Levi homozygotes
absent malleus head ( J:104286 )
• at P0, double homozygotes display absence of caput mallei
abnormal otic capsule morphology ( J:104286 )
• at birth, the vestibular portion of the otic capsule is always malformed, similar to Dlx5tm1Levi homozygotes

respiratory system
abnormal nasal capsule morphology ( J:104286 )
• at P0, double homozygotes display hypoplasia and asymmetry of the nasal capsules, similar to Dlx5tm1Levi homozygotes


Mouse Genome Informatics
cx12
     Barx1tm1Shiv/Barx1tm1Shiv
Msx1tm1Bero/Msx1+
involves: 129P2/OlaHsd * various
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
craniofacial
arrest of tooth development ( J:180393 )
• permanent in molars at the bud stage