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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Msx2tm1Rilm
targeted mutation 1, Richard Maas
MGI:1926381
Summary 14 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Msx2tm1Rilm/Msx2tm1Rilm either: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6J) MGI:2175121
hm2
Msx2tm1Rilm/Msx2tm1Rilm involves: 129S4/SvEvJae * BALB/c * C57BL/6 MGI:3050881
hm3
Msx2tm1Rilm/Msx2tm1Rilm involves: 129S4/SvJae MGI:4844283
hm4
Msx2tm1Rilm/Msx2tm1Rilm involves: 129S4/SvJae * BALB/c * CD-1 MGI:5649268
hm5
Msx2tm1Rilm/Msx2tm1Rilm involves: 129S4/SvJae * CD-1 MGI:5521204
ht6
Msx2tm1Rilm/Msx2+ involves: 129S4/SvEvJae * BALB/c * C57BL/6 MGI:3050889
cn7
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Msx2tm1Rilm/Msx2tm1Rilm
H2afvTg(Wnt1-cre)11Rth/0
involves: 129S4/SvJae * C57BL/6J * CBA/J MGI:5427701
cx8
Msx2tm1Rilm/Msx2+
Twist1tm1Bhr/Twist1+
involves: 129S4/SvEvJae * 129S7/SvEvBrd * BALB/c * C57BL/6 MGI:3050895
cx9
Foxn1nu/Foxn1nu
Msx2tm1Rilm/Msx2tm1Rilm
involves: 129S4/SvJae * BALB/c * CD-1 MGI:5521205
cx10
Msx1tm1Rilm/Msx1tm1Rilm
Msx2tm1Rilm/Msx2tm1Rilm
involves: 129S4/SvJae * BALB/c * CD-1 MGI:3050786
cx11
Msx1tm1Rilm/Msx1tm1Rilm
Msx2tm1Rilm/Msx2+
involves: 129S4/SvJae * CD-1 MGI:3050865
cx12
Msx1tm1Rilm/Msx1tm1Rilm
Msx2tm1Rilm/Msx2tm1Rilm
involves: 129S4/SvJae * CD-1 MGI:5528466
cx13
Msx1tm1Rilm/Msx1+
Msx2tm1Rilm/Msx2tm1Rilm
involves: 129S4/SvJae * CD-1 MGI:3050863
cx14
Msx2tm1Rilm/Msx2tm1Rilm
Tg(Pax6-cre,GFP)1Pgr/0
involves: 129S4/SvJae * FVB MGI:5427700


Genotype
MGI:2175121
hm1
Allelic
Composition
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
either: (involves: 129S4/SvJae) or (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6J)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• homozygotes are alive when kept on a protein-rich liquid diet

behavior/neurological
N
• homozygotes are not ataxic
• between 3 weeks and 2 months of age, mutants exhibit generalized seizures characterized by 3-min periods of often unilateral, myotonic limb extension, after which the mice recover

craniofacial
• at E18, homozygotes display a delay in frontal bone growth and interparietal and supraoccipital bone ossification
• in adult homozygotes, the mutant calvarium contains a significant midline foramen spanning the frontal bones
• frontal bone thickness is decreased anterior to the foramen
• the interparietal bone appears small and misshapen relative to wild-type
• the supraoccipital bone appears small and misshapen relative to wild-type
• mutant molars display severe degeneration, resulting in inability to chew solid food
• ameloblasts form, but undergo a progressive, TUNEL-negative degeneration after P1
• by P9, the ameloblast layer contains cellular debris and inflammatory cells, and only small amounts of enamel have accumulated
• at E16.5, homozygotes show a small reduction in enamel organ volume
• by P1, only a compact accumulation of epithelial cells is found in the mutant intercuspal regions; these cells abut the ameloblast layer and the stratum intermedium becomes indistinguishable
• at E17.5, the stellate reticulum is reduced in volume
• by P1, a discrete stratum intermedium is not identifiable
• mutant incisor teeth are brittle
• mutant incisor teeth are misaligned

endocrine/exocrine glands
• ~30% of mutant females exhibit abnormal mammary development
• in female neonates, mammary epithelial development arrests at the mammary sprout stage, developmentally equivalent to E16.5

limbs/digits/tail
• the mutant femur length is 83% that of wild-type
• the mutant tibia length is 88% that of wild-type

skeleton
• tartrate-resistant acid phosphatase staining is diminished in the mutant proximal tibia, suggesting reduced osteoclast numbers
• by P30, the numbers of osteoblasts at the epiphysis are decreased
• in mutants, axial and appendicular skeletal lengths are reduced relative to wild-type
• the mutant femur length is 83% that of wild-type
• the mutant tibia length is 88% that of wild-type
• the cell size of hypertrophic chondrocytes is reduced resulting in a smaller growth plate
• in mutants, axial and appendicular skeletal lengths are reduced relative to wild-type
• at E18, homozygotes display a delay in frontal bone growth and interparietal and supraoccipital bone ossification
• in adult homozygotes, the mutant calvarium contains a significant midline foramen spanning the frontal bones
• frontal bone thickness is decreased anterior to the foramen
• the interparietal bone appears small and misshapen relative to wild-type
• the supraoccipital bone appears small and misshapen relative to wild-type
• mutant molars display severe degeneration, resulting in inability to chew solid food
• ameloblasts form, but undergo a progressive, TUNEL-negative degeneration after P1
• by P9, the ameloblast layer contains cellular debris and inflammatory cells, and only small amounts of enamel have accumulated
• at E16.5, homozygotes show a small reduction in enamel organ volume
• by P1, only a compact accumulation of epithelial cells is found in the mutant intercuspal regions; these cells abut the ameloblast layer and the stratum intermedium becomes indistinguishable
• at E17.5, the stellate reticulum is reduced in volume
• by P1, a discrete stratum intermedium is not identifiable
• mutant incisor teeth are brittle
• mutant incisor teeth are misaligned
• the osteoblast defect appears to predominate as mutants are osteopenic
• at P30, mutant tibias show reduced cortical bone thickness
• by P30, cancellous bone is reduced
• by P30, the numbers of resting, proliferative and hypertrophic chondrocytes are decreased
• by P30, homozygotes exhibit osteochondrodystrophy i.e. abnormal cartilage and endochondral bone formation
• in homozygotes, BrdU-labelled osteoprogenitors in osteogenic fronts are reduced by 46% and 51% at P0 and P4, respectively

nervous system
N
• homozygotes display no cerebral phenotype
• between 3 weeks and 2 months of age, mutants exhibit generalized seizures characterized by 3-min periods of often unilateral, myotonic limb extension, after which the mice recover
• homozygotes show a reduction in the number of cerebellar lobules
• homozygotes show a lamination failure of the PCL
• homozygotes show a lamination failure of the IGL
• Purkinje cells are present but fail to coalesce into a discrete PCL, and the IGL is not compacted
• mutants display disorganized hemispheral and anterior vermal lobules
• the mutant vermis lacks a posterior lobule corresponding to the pyramis
• the mutant vermis is hypoplastic

hematopoietic system
• tartrate-resistant acid phosphatase staining is diminished in the mutant proximal tibia, suggesting reduced osteoclast numbers
• by P30, the numbers of osteoblasts at the epiphysis are decreased

immune system
• tartrate-resistant acid phosphatase staining is diminished in the mutant proximal tibia, suggesting reduced osteoclast numbers
• by P30, the numbers of osteoblasts at the epiphysis are decreased

integument
N
• mutant pups show normal whisker pad histology, innervation, and whisker-related pattern formation along the trigeminal pathway
• ~30% of mutant females exhibit abnormal mammary development
• in female neonates, mammary epithelial development arrests at the mammary sprout stage, developmentally equivalent to E16.5
• beginning at P14, homozygotes loose their pelage, becoming nude except for the snout and peri-orbital regions
• pelage regrowth occurs, but premature loss also occurs for the second coat, followed again by regrowth; thereafter, hair loss is patchy
• hair loss is temporally associated with premature entry into the catagen phase of the hair growth cycle
• at P5, mutant whiskers are curly
• at P5, mutant whiskers appear short and stubby

hearing/vestibular/ear

growth/size/body
• mutant molars display severe degeneration, resulting in inability to chew solid food
• ameloblasts form, but undergo a progressive, TUNEL-negative degeneration after P1
• by P9, the ameloblast layer contains cellular debris and inflammatory cells, and only small amounts of enamel have accumulated
• at E16.5, homozygotes show a small reduction in enamel organ volume
• by P1, only a compact accumulation of epithelial cells is found in the mutant intercuspal regions; these cells abut the ameloblast layer and the stratum intermedium becomes indistinguishable
• at E17.5, the stellate reticulum is reduced in volume
• by P1, a discrete stratum intermedium is not identifiable
• mutant incisor teeth are brittle
• mutant incisor teeth are misaligned

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
parietal foramina DOID:0060285 OMIM:168500
OMIM:609566
OMIM:609597
J:61509




Genotype
MGI:3050881
hm2
Allelic
Composition
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
involves: 129S4/SvEvJae * BALB/c * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
craniofacial
• no significant apoptosis is observed in mutant frontal bone osteogenic cells relative to wild-type
• at E12.5, neural crest precursor cells are present in normal numbers in the frontal bone anlagen; however, fewer cells express osteoblastic markers
• by E14.5, proliferation of a group of skeletogenic mesenchyme cells in the frontal bone rudiment is reduced

skeleton
• no significant apoptosis is observed in mutant frontal bone osteogenic cells relative to wild-type
• at E12.5, neural crest precursor cells are present in normal numbers in the frontal bone anlagen; however, fewer cells express osteoblastic markers
• by E14.5, proliferation of a group of skeletogenic mesenchyme cells in the frontal bone rudiment is reduced




Genotype
MGI:4844283
hm3
Allelic
Composition
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• eye defects are seen as early as E10.5
• eyes at 3 weeks of age show iris hyperplasia
• cornea edema
• severity of cornea defects in the eyes vary among animals
• eyes at 3 weeks of age show iridocorneal adhesion
• eyes at 3 weeks after birth have thickened corneas
• eyes have only a single layer of cornea epithelium cell
• corneal thickness is increased mainly in the stromal layer
• the lens is pushed toward the cornea by overproliferated retina and mesenchyme tissues
• severity of lens defects in the eyes vary among animals
• eyes at 3 weeks of age have a smaller lens in the anterior segment
• by E11.5, abnormal development of the eyes is seen with anterior expansion of the retinal pigmented epithelium
• the lens vesicle at E10.5 is smaller and incompletely developed
• the lens vesicle is compressed by the invading periocular mesenchyme
• optic vesicle at E10.5 is larger than in wild-type mice
• enucleated eyes of mutants at 3 months of age are microphthalmic and about 50% smaller in size than wild-type eyes
• smaller palpebral fissure
• folding of the retina
• by E11.5, abnormal development of the eyes is seen with anterior expansion of the retinal pigmented epithelium
• the anterior movement of the retinal pigmented epithelium results in an iris with a bowtie-like appearance
• presence of ectopic pigmented tissue in the vitreous

pigmentation
• by E11.5, abnormal development of the eyes is seen with anterior expansion of the retinal pigmented epithelium
• the anterior movement of the retinal pigmented epithelium results in an iris with a bowtie-like appearance




Genotype
MGI:5649268
hm4
Allelic
Composition
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
involves: 129S4/SvJae * BALB/c * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
N
• defects in atrioventricular cushions and valves are not seen unlike in mice homozygous for this allele and Msx1tm1Rilm




Genotype
MGI:5521204
hm5
Allelic
Composition
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
involves: 129S4/SvJae * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• nail phenotype is 100% penetrant
• decreased expression of some acidic and basic keratins in the keratogenous zone
• fragile nails that are frequently cracked




Genotype
MGI:3050889
ht6
Allelic
Composition
Msx2tm1Rilm/Msx2+
Genetic
Background
involves: 129S4/SvEvJae * BALB/c * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
craniofacial
• heterozygotes exhibit a frontal foramen phenotype that is intermediate in severity relative to wild-type and homozygous mutant mice

skeleton
• heterozygotes exhibit a frontal foramen phenotype that is intermediate in severity relative to wild-type and homozygous mutant mice




Genotype
MGI:5427701
cn7
Allelic
Composition
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Msx2tm1Rilm/Msx2tm1Rilm
H2afvTg(Wnt1-cre)11Rth/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1Sor mutation (7 available); any Gt(ROSA)26Sor mutation (492 available)
H2afvTg(Wnt1-cre)11Rth mutation (2 available); any H2afv mutation (20 available)
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• persistent adherence of the lens vesicle to the corneal ectoderm hinders the migration of neural crest cells across the stromal space between the surface ectoderm and endothelium




Genotype
MGI:3050895
cx8
Allelic
Composition
Msx2tm1Rilm/Msx2+
Twist1tm1Bhr/Twist1+
Genetic
Background
involves: 129S4/SvEvJae * 129S7/SvEvBrd * BALB/c * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
Twist1tm1Bhr mutation (4 available); any Twist1 mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
craniofacial
• in double heterozygotes, the frontal foramen phenotype is 3x more severe than in either single heterozygote

limbs/digits/tail
• in double heterozygotes, the incidence of digit duplication is identical to that observed in Twist1tm1Bhr heterozygotes (34%)

skeleton
• in double heterozygotes, the frontal foramen phenotype is 3x more severe than in either single heterozygote

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Saethre-Chotzen syndrome DOID:14768 OMIM:101400
J:87044




Genotype
MGI:5521205
cx9
Allelic
Composition
Foxn1nu/Foxn1nu
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
involves: 129S4/SvJae * BALB/c * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxn1nu mutation (30 available); any Foxn1 mutation (49 available)
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• nail phenotype is 100% penetrant
• hyperplastic with multiple layers of cells with no visible transition from nail matrix to nail bed
• distal matrix hyperproliferation
• rugged surface with irregular squames
• broken with blunt ends
• break beyond the hyponychium
• break is more proximal than in Foxn1nu single mutants




Genotype
MGI:3050786
cx10
Allelic
Composition
Msx1tm1Rilm/Msx1tm1Rilm
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
involves: 129S4/SvJae * BALB/c * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx1tm1Rilm mutation (1 available); any Msx1 mutation (6 available)
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• only sparse mesenchymal cells expression alpha-SMA are found in atrioventricular cushions indicating a defect in EMT
• deformed at E14.5 and E16.5
• at E14.5 and E16.5
• deformed valves at E14.5 and E16.5
• shorter but thicker valves indicating a failure of valve outgrowth and remodeling

craniofacial
• double mutant embryos that survive until late gestation display no calvarial ossification; in contrast, the chondrocranium is preserved
• in double homozygotes, tooth development arrests at the lamina or early bud stages, i.e. earlier than the bud stage arrest observed in Msx1tm1Rilm mutants

endocrine/exocrine glands
• all male and female double homozygotes show a failure of mammary epithelial invagination, resulting in subsequent regression

skeleton
• double mutant embryos that survive until late gestation display no calvarial ossification; in contrast, the chondrocranium is preserved
• in double homozygotes, tooth development arrests at the lamina or early bud stages, i.e. earlier than the bud stage arrest observed in Msx1tm1Rilm mutants

integument
• all male and female double homozygotes show a failure of mammary epithelial invagination, resulting in subsequent regression
• at E18.5, the number of hair follicles in double-mutant dorsal back skin is reduced to ~1/3 that of wild-type

growth/size/body
• in double homozygotes, tooth development arrests at the lamina or early bud stages, i.e. earlier than the bud stage arrest observed in Msx1tm1Rilm mutants




Genotype
MGI:3050865
cx11
Allelic
Composition
Msx1tm1Rilm/Msx1tm1Rilm
Msx2tm1Rilm/Msx2+
Genetic
Background
involves: 129S4/SvJae * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx1tm1Rilm mutation (1 available); any Msx1 mutation (6 available)
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hearing/vestibular/ear
N
• compound mutants display formation of the malleal manubrium




Genotype
MGI:5528466
cx12
Allelic
Composition
Msx1tm1Rilm/Msx1tm1Rilm
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
involves: 129S4/SvJae * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx1tm1Rilm mutation (1 available); any Msx1 mutation (6 available)
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
craniofacial
• at E14.5, the body of the malleus is reduced and remains attached to a malformed Meckel's cartilage
• at E14.5, the malleal manubrium is absent
• at E14.5, the malleal processus brevis is absent
• at E14.5, the body of the malleus is smaller than normal
• double homozygotes show a stronger hypomorphism of the malleus relative to single Msx1tm1Rilm mutants
• at E14.5, the Meckel's cartilage displays a curvature at the caudal end
• at E14.5 and E15.5, double homozygotes lack an external acoustic meatus opening

hearing/vestibular/ear
• at E14.5, the body of the malleus is reduced and remains attached to a malformed Meckel's cartilage
• at E14.5, the malleal manubrium is absent
• at E14.5, the malleal processus brevis is absent
• at E14.5, the body of the malleus is smaller than normal
• double homozygotes show a stronger hypomorphism of the malleus relative to single Msx1tm1Rilm mutants
• at E14.5 and E15.5, double homozygotes lack an external acoustic meatus opening
• at E14.5 and E15.5, the tympanic ring is not found

skeleton
• at E14.5, the body of the malleus is reduced and remains attached to a malformed Meckel's cartilage
• at E14.5, the malleal manubrium is absent
• at E14.5, the malleal processus brevis is absent
• at E14.5, the body of the malleus is smaller than normal
• double homozygotes show a stronger hypomorphism of the malleus relative to single Msx1tm1Rilm mutants
• at E14.5, the Meckel's cartilage displays a curvature at the caudal end

growth/size/body
• at E14.5 and E15.5, double homozygotes lack an external acoustic meatus opening




Genotype
MGI:3050863
cx13
Allelic
Composition
Msx1tm1Rilm/Msx1+
Msx2tm1Rilm/Msx2tm1Rilm
Genetic
Background
involves: 129S4/SvJae * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx1tm1Rilm mutation (1 available); any Msx1 mutation (6 available)
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hearing/vestibular/ear
N
• compound mutants display normal development of the malleus in the middle ear




Genotype
MGI:5427700
cx14
Allelic
Composition
Msx2tm1Rilm/Msx2tm1Rilm
Tg(Pax6-cre,GFP)1Pgr/0
Genetic
Background
involves: 129S4/SvJae * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Msx2tm1Rilm mutation (1 available); any Msx2 mutation (12 available)
Tg(Pax6-cre,GFP)1Pgr mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• at E12.5, the cornea and lens are not separated
• at E12.5, the neural crest cells migrate into the vitreous cavity and push the lens toward the cornea while in wild-type mice, the lens vesicle and surface ectoderm are completely separated





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last database update
05/14/2019
MGI 6.14
The Jackson Laboratory