Phenotypes associated with this allele

• Allele Symbol: Runx2^tm1Mjo
• Allele Name: targeted mutation 1, Michael J Owen
• Allele ID: MGI:2176465
• Summary: 20 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Runx2^tm1Mjo/Runx2^tm1Mjo	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3044748
hm2	Runx2^tm1Mjo/Runx2^tm1Mjo	involves: C57BL/6 * NMRI	MGI:3055822
hm3	Runx2^tm1Mjo/Runx2^tm1Mjo	Not Specified	MGI:4440961
ht4	Runx2^tm1Mjo/Runx2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3044747
ht5	Runx2^tm1Mjo/Runx2^+	Not Specified	MGI:4887970
cn6	Gt(ROSA)26Sor^tm3(Runx2)Flng/Gt(ROSA)26Sor^tm3(Runx2)Flng Runx2^tm1Mjo/Runx2^tm1Mjo Tg(Col2a1-cre)3Amc/0	involves: 129X1/SvJ	MGI:5311112
cn7	Gt(ROSA)26Sor^tm3(Runx2)Flng/Gt(ROSA)26Sor^+ Runx2^tm1Mjo/Runx2^tm1Mjo Tg(Col2a1-cre)3Amc/0	involves: 129X1/SvJ	MGI:5311113
cn8	Runx1^tm1.1Stkd/Runx1^tm1.1Stkd Runx2^tm1Mjo/Runx2^tm1Mjo Tg(Col2a1-cre)1Star/0	involves: C57BL/6	MGI:4440962
cn9	Runx1^tm1.1Stkd/Runx1^tm1.1Stkd Runx2^tm1Mjo/Runx2^tm1Mjo Tg(Prrx1-cre)1Cjt/0	involves: C57BL/6J * SJL/J	MGI:4440959
cn10	Runx2^tm1Mjo/Runx2^+ Runx3^tm3Yg/Runx3^tm3Yg Tg(Col1a1-cre)1Kry/0	involves: FVB/N	MGI:5689562
cx11	Flnb^Gt(XD076)Byg/Flnb^Gt(XD076)Byg Runx2^tm1Mjo/Runx2^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3785402
cx12	Runx2^tm1Mjo/Runx2^+ Runx3^tm1Yg/Runx3^tm1Yg	involves: 129S1/Sv * 129X1/SvJ * ICR	MGI:5689554
cx13	Tle5^tm1Grid/Tle5^tm1Grid Runx2^tm1Mjo/Runx2^+	involves: 129S1/Sv * C57BL/6	MGI:3582296
cx14	Runx2^tm1Mjo/Runx2^+ Twist1^tm1Bhr/Twist1^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3582479
cx15	Runx2^tm1Mjo/Runx2^+ Twist2^tm1(cre)Dor/Twist2^tm1(cre)Dor	involves: 129X1/SvJ * C57BL/6	MGI:3582480
cx16	Runx2^tm1Mjo/Runx2^+ Twist2^tm1(cre)Dor/Twist2^+	involves: 129X1/SvJ * C57BL/6	MGI:3582481
cx17	Hivep3^tm1Glm/Hivep3^tm1Glm Runx2^tm1Mjo/Runx2^+	involves: C57BL/6	MGI:5550514
cx18	Runx2^tm1Mjo/Runx2^+ Tg(Eno2tTA)#Nes/0 Tg(tetO-Zfp521)#Rbar/0	involves: C57BL/6 * SJL	MGI:4887973
cx19	Runx2^tm1Mjo/Runx2^+ Satb2^tm1Rug/Satb2^+	Not Specified	MGI:3696662
cx20	Runx2^tm1Mjo/Runx2^+ Zfp521^tm2Ngc/Zfp521^+	Not Specified	MGI:4887971

Genotype
MGI:3044748

hm1

• Allelic Composition: Runx2^tm1Mjo/Runx2^tm1Mjo
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

mortality/aging

neonatal lethality, complete penetrance ( J:40784 )

• homozygotes die of respiratory failure shortly after birth

skeleton

abnormal cranium morphology ( J:40784 )

• at 19.5 dpc, mutant skulls have thinner cartilaginous plates than wild-type skulls

abnormal tooth development ( J:40784 )

• in homozygotes, the tooth primordia are severely hypoplastic; however, differentiation into the different layers proceeds normally

abnormal clavicle morphology ( J:40784 )

• at 19.5 dpc, homozygotes lack a cellular clavicular mesenchyme; as a result, no cartilaginous head is identified

decreased osteoblast cell number ( J:40784 )

• at 17.5 dpc, homozygotes fail to exhibit detectable osteoblastic differentiation and lack ossification centers or marrow formation

• at this stage, the mesenchymal cell layer is small and inactive, and osteoblasts are absent

abnormal cartilage development ( J:40784 )

• at 19.5 dpc, the cartilage appears underdeveloped but displays some organization into growth plates near the diaphyseal end plates

• no osteoid is detected; however, a patchy calcification of cartilaginous tissue matrix is noted in the femur, tibia, and vertebrae, resulting in a reticulated pattern in the diaphyseal regions

abnormal bone ossification ( J:40784 )

• at 17.5 dpc, homozygotes display an almost complete absence of ossification of the entire skeleton; in contrast, cartilage formation appears unaffected

• at birth, homozygotes exhibit small areas of mineralization; however, these areas do not correspond to any ossification

delayed endochondral bone ossification ( J:40784 )

delayed intramembranous bone ossification ( J:40784 )

• at 19.5 dpc, the cellular mesenchymal layer that gives rise to intramembranous ossification is absent in mutant skulls

craniofacial

abnormal cranium morphology ( J:40784 )

• at 19.5 dpc, mutant skulls have thinner cartilaginous plates than wild-type skulls

abnormal tooth development ( J:40784 )

• in homozygotes, the tooth primordia are severely hypoplastic; however, differentiation into the different layers proceeds normally

abnormal nose morphology ( J:40784 )

• from ~E16.5 dpc onwards, homozygotes display a foreshortened nose

respiratory system

pulmonary vascular congestion ( J:40784 )

• live-born homozygotes exhibit vascular congestion of the lungs

abnormal nose morphology ( J:40784 )

• from ~E16.5 dpc onwards, homozygotes display a foreshortened nose

abnormal lung volume ( J:40784 )

• in live-born homozygotes, lungs appear underinflated despite normal bronchio-alveolar development; lung morphology is consistent with death due to asphyxia

respiratory failure ( J:40784 )

• most homozygotes delivered by Caesarean section at 18.5 or 19.5 dpc live; however, some pups occasionally gasp for air at irregular intervals, and show no signs of life after 20 minutes

hematopoietic system

absent bone marrow cell ( J:40784 )

• newborn homozygotes display no formation of marrow cavities: vascularization and population of the marrow by hematopoetic cells fails

increased nucleated erythrocyte cell number ( J:40784 )

• at 16.5 dpc, homozygotes display a 10- to 100-fold rise in primitive nucleated erythrocytes relative to wild-type mice

• the increase in primitive nucleated erythrocytes is likely to be a secondary effect of absence of hemotopoietic marrow development

growth/size/body

abnormal tooth development ( J:40784 )

• in homozygotes, the tooth primordia are severely hypoplastic; however, differentiation into the different layers proceeds normally

abnormal nose morphology ( J:40784 )

• from ~E16.5 dpc onwards, homozygotes display a foreshortened nose

decreased body size ( J:40784 )

• homozygotes are small relative to wild-type mice

decreased body weight ( J:40784 )

• the weight of homozygous mutant mice is reduced by approximately one-third relative to the weight of wild-type mice

cardiovascular system

pulmonary vascular congestion ( J:40784 )

• live-born homozygotes exhibit vascular congestion of the lungs

Genotype
MGI:3055822

hm2

• Allelic Composition: Runx2^tm1Mjo/Runx2^tm1Mjo
• Genetic Background: involves: C57BL/6 * NMRI

craniofacial

abnormal molar morphology ( J:87161 )

• in homozygotes, mandibular molar organs are more severely affected than maxillary molar organs

• at E18, the dental lamina of mutant mandibles is highly proliferative, with no clear progression to the cap stage; in contrast, maxillary molar organs advance to the bud stage

abnormal dental lamina morphology ( J:87161 )

• at E18, the dental lamina of mutant mandibles is highly proliferative, with no clear advancement to the cap stage

abnormal dental papilla morphology ( J:87161 )

• mesenchymal dental papilla fails to form

abnormal cervical loop morphology ( J:87161 )

• epithelial cervical loops fail to form

abnormal enamel knot morphology ( J:87161 )

• mutant molar organs lack a morphologically distinguishable enamel knot

arrest of tooth development ( J:87161 )

• homozygotes display a developmental arrest in tooth morphogenesis in the transition from the bud to the cap stage

growth retardation of incisors ( J:87161 )

• mutant maxillary and mandibular incisor organs are less severly affected than molar organs but show poorly differentiated odontoblasts and ameloblasts

growth retardation of molars ( J:87161 )

• at E13 (early bud stage), homozygotes display a delay in maxillary molar development relative to wild-type mice

• at E14, wild-type molar organs have reached the cap stage with an enamel knot and cervical loops; in contrast, mutant E14 molars have not progressed beyond the bud stage of E13

• at E16 (early bell-stage), homozygotes exhibit extra buddings in the anterior and palatal aspects of upper maxillary molars relative to wild-type; such accessory outgrowths are also found in lower molars

• at E18, the tooth buds of mutant molars have regressed; the extra buddings are indistinguishable from the actual tooth organ and the mandibular lamina is irregular

palatal shelves fail to meet at midline ( J:87161 )

• most newborn mutants show a failure of fusion between the shelves of the secondary palate

• palatal clefting is not associated with defects in primary palate fusion or cleft lip

cleft secondary palate ( J:87161 )

skeleton

abnormal molar morphology ( J:87161 )

• in homozygotes, mandibular molar organs are more severely affected than maxillary molar organs

• at E18, the dental lamina of mutant mandibles is highly proliferative, with no clear progression to the cap stage; in contrast, maxillary molar organs advance to the bud stage

abnormal dental lamina morphology ( J:87161 )

• at E18, the dental lamina of mutant mandibles is highly proliferative, with no clear advancement to the cap stage

abnormal dental papilla morphology ( J:87161 )

• mesenchymal dental papilla fails to form

abnormal cervical loop morphology ( J:87161 )

• epithelial cervical loops fail to form

abnormal enamel knot morphology ( J:87161 )

• mutant molar organs lack a morphologically distinguishable enamel knot

arrest of tooth development ( J:87161 )

• homozygotes display a developmental arrest in tooth morphogenesis in the transition from the bud to the cap stage

growth retardation of incisors ( J:87161 )

• mutant maxillary and mandibular incisor organs are less severly affected than molar organs but show poorly differentiated odontoblasts and ameloblasts

growth retardation of molars ( J:87161 )

• at E13 (early bud stage), homozygotes display a delay in maxillary molar development relative to wild-type mice

• at E14, wild-type molar organs have reached the cap stage with an enamel knot and cervical loops; in contrast, mutant E14 molars have not progressed beyond the bud stage of E13

• at E16 (early bell-stage), homozygotes exhibit extra buddings in the anterior and palatal aspects of upper maxillary molars relative to wild-type; such accessory outgrowths are also found in lower molars

• at E18, the tooth buds of mutant molars have regressed; the extra buddings are indistinguishable from the actual tooth organ and the mandibular lamina is irregular

vision/eye

eyelids open at birth ( J:87161 )

• several mutant pups fail to exhibit eyelid closure at the neonatal stage

digestive/alimentary system

palatal shelves fail to meet at midline ( J:87161 )

• most newborn mutants show a failure of fusion between the shelves of the secondary palate

• palatal clefting is not associated with defects in primary palate fusion or cleft lip

cleft secondary palate ( J:87161 )

growth/size/body

abnormal molar morphology ( J:87161 )

• in homozygotes, mandibular molar organs are more severely affected than maxillary molar organs

• at E18, the dental lamina of mutant mandibles is highly proliferative, with no clear progression to the cap stage; in contrast, maxillary molar organs advance to the bud stage

abnormal dental lamina morphology ( J:87161 )

• at E18, the dental lamina of mutant mandibles is highly proliferative, with no clear advancement to the cap stage

abnormal dental papilla morphology ( J:87161 )

• mesenchymal dental papilla fails to form

abnormal cervical loop morphology ( J:87161 )

• epithelial cervical loops fail to form

abnormal enamel knot morphology ( J:87161 )

• mutant molar organs lack a morphologically distinguishable enamel knot

arrest of tooth development ( J:87161 )

• homozygotes display a developmental arrest in tooth morphogenesis in the transition from the bud to the cap stage

growth retardation of incisors ( J:87161 )

• mutant maxillary and mandibular incisor organs are less severly affected than molar organs but show poorly differentiated odontoblasts and ameloblasts

growth retardation of molars ( J:87161 )

• at E13 (early bud stage), homozygotes display a delay in maxillary molar development relative to wild-type mice

• at E14, wild-type molar organs have reached the cap stage with an enamel knot and cervical loops; in contrast, mutant E14 molars have not progressed beyond the bud stage of E13

• at E16 (early bell-stage), homozygotes exhibit extra buddings in the anterior and palatal aspects of upper maxillary molars relative to wild-type; such accessory outgrowths are also found in lower molars

• at E18, the tooth buds of mutant molars have regressed; the extra buddings are indistinguishable from the actual tooth organ and the mandibular lamina is irregular

palatal shelves fail to meet at midline ( J:87161 )

• most newborn mutants show a failure of fusion between the shelves of the secondary palate

• palatal clefting is not associated with defects in primary palate fusion or cleft lip

cleft secondary palate ( J:87161 )

Genotype
MGI:4440961

hm3

• Allelic Composition: Runx2^tm1Mjo/Runx2^tm1Mjo
• Genetic Background: Not Specified

skeleton

abnormal incisor morphology ( J:54817 )

• at birth, mutant incisors display poorly differentiated odontoblasts

small incisors ( J:54817 )

• at E16.5, homozygous mutant incisors are significantly hypoplastic relative to wild-type incisors

small molars ( J:54817 )

• at E16.5, homozygous mutant molars are significantly hypoplastic relative to wild-type molars

growth retardation of incisors ( J:54817 )

• at E16.5, homozygous mutant incisors appear developmentally retarded relative to wild-type incisors; abnormal tissue separation is noted at the epithelial-mesenchymal interface

growth retardation of molars ( J:54817 )

• at birth, mutant molar organs are still at the cap/early bell stage as opposed to the late bell stage in wild-type molars

abnormal dentin morphology ( J:54817 )

• at birth, mutant incisors display a highly disorganized dentin matrix relative to wild-type

abnormal enamel morphology ( J:54817 )

• at E16.5 and birth, mutant molars and incisors show poor differentiation of the enamel, which has only advanced to the cap stage

• at birth, the abnormal enamel organ of first molars displays poorly discernible cuspal outlines; the peripheral layer of cells in the dental papilla show no polarization

abnormal humerus morphology ( J:53540 )

• at E17.5, mutant humeri, but not mutant radii, display absence of chondrocyte hypertrophy and ossification

abnormal radius morphology ( J:53540 )

• at E17.5, mutant radii exhibit delayed and severely reduced chondrocyte hypertrophy relative to wild-type

abnormal ulna morphology ( J:53540 )

• at E17.5, mutant ulnae exhibit delayed and severely reduced chondrocyte hypertrophy relative to wild-type

abnormal xiphoid process morphology ( J:158761 )

• not mineralized in newborn mice

abnormal chondrocyte morphology ( J:53540 )

• at E17.5, homozygotes display lack of chondrocyte differentiation and hypertrophy, with the proximal limb segments being most severely affected

• at E17.5, chondrocyte morphology of mutant humeri and phalanges resembles that of wild-type mice at E13 dpc (pre-hypertrophic)

• in radius/ulna some hypertrophic cells are detected by E14.5 to E15.5 and calcified cartilage is observed at E17.5

abnormal skeleton development ( J:158761 )

• at E14.5, sternal bar development is delayed compared to in wild-type mice

abnormal long bone epiphyseal plate morphology ( J:53540 )

• homozygotes display altered growth plate architecture, despite normal development of the initial cartilaginous anlage in all skeletal segments

abnormal long bone hypertrophic chondrocyte zone ( J:158761 )

abnormal cartilage development ( J:53540 )

• homozygotes display loss or severe retardation of cartilage calcification relative to wild-type mice; no vascular invasion is noted in areas of calcified cartilage

delayed endochondral bone ossification ( J:53540 )

• at E17.5, homozygotes show no ossification with the exception of radius/ulna and tibia/fibula; here, calcification is not detectable until E16.5, whereas wild-type mice display calcification as early as E14.5

cardiovascular system

decreased angiogenesis ( J:158761 )

• at E17.5, homozygotes display no vessel invasion into cartilage, in spite of abundant vascularization in the perichondrium and the surrounding tissue

• absence of cartilage angiogenesis is associated with lack of VEGF upregulation in hypertrophic chondrocytes, and no upregulation of the expression of VEGF receptors in perichondrial endothelial cells

craniofacial

abnormal incisor morphology ( J:54817 )

• at birth, mutant incisors display poorly differentiated odontoblasts

small incisors ( J:54817 )

• at E16.5, homozygous mutant incisors are significantly hypoplastic relative to wild-type incisors

small molars ( J:54817 )

• at E16.5, homozygous mutant molars are significantly hypoplastic relative to wild-type molars

growth retardation of incisors ( J:54817 )

• at E16.5, homozygous mutant incisors appear developmentally retarded relative to wild-type incisors; abnormal tissue separation is noted at the epithelial-mesenchymal interface

growth retardation of molars ( J:54817 )

• at birth, mutant molar organs are still at the cap/early bell stage as opposed to the late bell stage in wild-type molars

abnormal dentin morphology ( J:54817 )

• at birth, mutant incisors display a highly disorganized dentin matrix relative to wild-type

abnormal enamel morphology ( J:54817 )

• at E16.5 and birth, mutant molars and incisors show poor differentiation of the enamel, which has only advanced to the cap stage

• at birth, the abnormal enamel organ of first molars displays poorly discernible cuspal outlines; the peripheral layer of cells in the dental papilla show no polarization

limbs/digits/tail

abnormal humerus morphology ( J:53540 )

• at E17.5, mutant humeri, but not mutant radii, display absence of chondrocyte hypertrophy and ossification

abnormal radius morphology ( J:53540 )

• at E17.5, mutant radii exhibit delayed and severely reduced chondrocyte hypertrophy relative to wild-type

abnormal ulna morphology ( J:53540 )

• at E17.5, mutant ulnae exhibit delayed and severely reduced chondrocyte hypertrophy relative to wild-type

growth/size/body

abnormal incisor morphology ( J:54817 )

• at birth, mutant incisors display poorly differentiated odontoblasts

small incisors ( J:54817 )

• at E16.5, homozygous mutant incisors are significantly hypoplastic relative to wild-type incisors

small molars ( J:54817 )

• at E16.5, homozygous mutant molars are significantly hypoplastic relative to wild-type molars

growth retardation of incisors ( J:54817 )

• at E16.5, homozygous mutant incisors appear developmentally retarded relative to wild-type incisors; abnormal tissue separation is noted at the epithelial-mesenchymal interface

growth retardation of molars ( J:54817 )

• at birth, mutant molar organs are still at the cap/early bell stage as opposed to the late bell stage in wild-type molars

abnormal dentin morphology ( J:54817 )

• at birth, mutant incisors display a highly disorganized dentin matrix relative to wild-type

abnormal enamel morphology ( J:54817 )

• at E16.5 and birth, mutant molars and incisors show poor differentiation of the enamel, which has only advanced to the cap stage

• at birth, the abnormal enamel organ of first molars displays poorly discernible cuspal outlines; the peripheral layer of cells in the dental papilla show no polarization

Genotype
MGI:3044747

ht4

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

integument

underdeveloped hair follicles ( J:132568 )

• there is a significantly reduced percentage of stage 4 follicles in E18.5- E19.0 embryos (23% vs 17% in wild-type controls at E18.5)

• there is also a significant reduction in stage 3 follicles at E19.0 (25% vs. 34%)

abnormal skin morphology ( J:132568 )

• the mean overall thickness of the skin of E18.5 embryos is 196 microns compared to 252 microns for wild-type embryos

abnormal epidermis suprabasal layer morphology ( J:132568 )

• there is a 37% reduction of basal epithelial cells that are actively dividing in the skin of E18.5 embyros compared to wild-type embryos

thin epidermis ( J:132568 )

• the mean thickness of the epidermis of E18.5 embryos is 35 microns which is significantly less than the mean of 43 microns for wild-type embryos

cellular

abnormal osteoblast differentiation ( J:40784 )

• heterozygotes exhibit neither surface osteoblastic differentiation nor intramembranous bone formation laterally

craniofacial

wide cranial sutures ( J:40784 )

• newborn heterozygotes display delayed ossification of the cranial bones resulting in widened cranial sutures

abnormal fontanelle morphology ( J:40784 )

• newborn heterozygotes display delayed ossification of the cranial bones resulting in an open anterior and posterior fontanelle

interparietal bone hypoplasia ( J:40784 )

• in newborn heterozygotes, the interparietal bones are hypoplastic relative to those of wild-type mice; numerous Wormian bones are present

parietal bone hypoplasia ( J:40784 )

• in newborn heterozygotes, the parietal bones are hypoplastic relative to those of wild-type mice; numerous Wormian bones are present

hyoid bone hypoplasia ( J:40784 )

• newborn heterozygotes have a hypoplastic hyoid bone with two distinct ossification centers

abnormal tooth development ( J:40784 )

• in heterozygotes, the development of tooth primordia is slightly retarded but otherwise normal

limbs/digits/tail

abnormal humerus morphology ( J:40784 )

absent deltoid tuberosity ( J:40784 )

• heterozygotes show loss of the deltoid tuberosity of the humerus

skeleton

abnormal osteoblast differentiation ( J:40784 )

• heterozygotes exhibit neither surface osteoblastic differentiation nor intramembranous bone formation laterally

wide cranial sutures ( J:40784 )

• newborn heterozygotes display delayed ossification of the cranial bones resulting in widened cranial sutures

abnormal fontanelle morphology ( J:40784 )

• newborn heterozygotes display delayed ossification of the cranial bones resulting in an open anterior and posterior fontanelle

interparietal bone hypoplasia ( J:40784 )

• in newborn heterozygotes, the interparietal bones are hypoplastic relative to those of wild-type mice; numerous Wormian bones are present

parietal bone hypoplasia ( J:40784 )

• in newborn heterozygotes, the parietal bones are hypoplastic relative to those of wild-type mice; numerous Wormian bones are present

hyoid bone hypoplasia ( J:40784 )

• newborn heterozygotes have a hypoplastic hyoid bone with two distinct ossification centers

abnormal tooth development ( J:40784 )

• in heterozygotes, the development of tooth primordia is slightly retarded but otherwise normal

abnormal humerus morphology ( J:40784 )

absent deltoid tuberosity ( J:40784 )

• heterozygotes show loss of the deltoid tuberosity of the humerus

clavicle hypoplasia ( J:40784 )

• newborn heterozygotes exhibit hypoplasia of the clavicle; only a clavicular (lateral) rudiment is observed

• heterozygous clavicles display a slightly hypoactive periclavicular mesenchyme with less advanced cartilaginous differentiation at 16.5 dpc, but with organizing cartilage at 19.5 dpc

abnormal xiphoid process morphology ( J:40784 )

• newborn heterozygotes have a wider xiphoid process of the sternum with two well-separated ossification centers

ischium hypoplasia ( J:40784 )

• the pubic and ischial bones are widely separated and hypoplastic in newborns

pubis hypoplasia ( J:40784 )

• the pubic and ischial bones are widely separated and hypoplastic in newborns

abnormal cartilage morphology ( J:40784 )

• adult heterozygotes have a solid cartilaginous bar within a thick fibrous sheath; the cartilage appears disorganized with no matrix calcification

abnormal long bone epiphyseal plate morphology ( J:40784 )

• in adult heterozygotes, epiphyseal growth-plate structure and differentiation are only slightly perturbed

delayed endochondral bone ossification ( J:40784 )

• at 16.5 dpc, heterozygous embryos show a slight delay in endochondral ossification, with relatively normal vascularization and population of the marrow by hematopoetic cells

delayed intramembranous bone ossification ( J:40784 )

• at 16.5 dpc, the skulls of heterozygotes have slightly thinner cartilage plates with minimal intramembranous ossification; however, ossification is readily detectable at 19.5 dpc

growth/size/body

abnormal tooth development ( J:40784 )

• in heterozygotes, the development of tooth primordia is slightly retarded but otherwise normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cleidocranial dysplasia		DOID:13994	OMIM:119600 OMIM:216330	J:40784 , J:53868

Genotype
MGI:4887970

ht5

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺
• Genetic Background: Not Specified

Trabecular bone and clavicle analysis in various mice with Runx2^tm1Mjo and/or Hivep3^tm1Glm alleles

skeleton

abnormal fontanelle morphology ( J:167992 )

• at P25, mice exhibit a defined nonmineralization area between the anterior and posterior fontanelles compared to in wild-type mice

abnormal hyoid bone morphology ( J:167992 )

• the midportion of the hyoid bone fails to mineralize unlike in wild-type mice

clavicle hypoplasia ( J:167992 , J:201597 )

craniofacial

abnormal fontanelle morphology ( J:167992 )

• at P25, mice exhibit a defined nonmineralization area between the anterior and posterior fontanelles compared to in wild-type mice

abnormal hyoid bone morphology ( J:167992 )

• the midportion of the hyoid bone fails to mineralize unlike in wild-type mice

Genotype
MGI:5311112

cn6

• Allelic Composition: Gt(ROSA)26Sor^{tm3(Runx2)Flng}/Gt(ROSA)26Sor^{tm3(Runx2)Flng}; Runx2^tm1Mjo/Runx2^tm1Mjo; Tg(Col2a1-cre)3Amc/0
• Genetic Background: involves: 129X1/SvJ

skeleton

skeleton phenotype ( J:180304 )

N • unlike Runx2^tm1Mjo homozygotes, mice exhibit normal cartilage, bone collar, and marrow and restored osteoblast differentiation and cartilage hypertrophy

abnormal bone ossification ( J:180304 )

• at E18.5, bone formation defects observed in Runx2^tm1Mjo homozygotes are partially recovered in the endochondrial skeleton but not the skull

Genotype
MGI:5311113

cn7

• Allelic Composition: Gt(ROSA)26Sor^{tm3(Runx2)Flng}/Gt(ROSA)26Sor⁺; Runx2^tm1Mjo/Runx2^tm1Mjo; Tg(Col2a1-cre)3Amc/0
• Genetic Background: involves: 129X1/SvJ

skeleton

skeleton phenotype ( J:180304 )

N • unlike Runx2^tm1Mjo homozygotes, mice exhibit normal bone collar

abnormal bone marrow cavity morphology ( J:180304 )

• like Runx2^tm1Mjo homozygotes, mice lack a marrow cavity

abnormal bone ossification ( J:180304 )

• at E18.5, bone formation defects observed in Runx2^tm1Mjo homozygotes are partially recovered in the endochondrial skeleton but not the skull

Genotype
MGI:4440962

cn8

• Allelic Composition: Runx1^tm1.1Stkd/Runx1^tm1.1Stkd; Runx2^tm1Mjo/Runx2^tm1Mjo; Tg(Col2a1-cre)1Star/0
• Genetic Background: involves: C57BL/6

skeleton

abnormal skeleton morphology ( J:158761 )

• newborn mice are indistinguishable from Runx2^tm1Mjo homozygotes

Genotype
MGI:4440959

cn9

• Allelic Composition: Runx1^tm1.1Stkd/Runx1^tm1.1Stkd; Runx2^tm1Mjo/Runx2^tm1Mjo; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: C57BL/6J * SJL/J

mortality/aging

preweaning lethality, complete penetrance ( J:158761 )

• mice are non-viable

skeleton

absent sternum ( J:158761 )

• in newborn mice with no sign of sternal bar development

abnormal skeleton development ( J:158761 )

• sternal bar development is absent unlike in wild-type mice

abnormal chondrocyte differentiation ( J:158761 )

• at E13.5, reduced Alcian blue staining of cartilaginous matrices and marker expression compared to in wild-type mice indicate impaired chondrocyte differentiation

abnormal bone mineralization ( J:158761 )

• mice fail to exhibit mineralization of most skeletal elements, including the sternum, unlike in wild-type mice

Genotype
MGI:5689562

cn10

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Runx3^tm3Yg/Runx3^tm3Yg; Tg(Col1a1-cre)1Kry/0
• Genetic Background: involves: FVB/N

growth/size/body

decreased body size ( J:224290 )

• dwarfism

decreased body height ( J:224290 )

• short stature

Genotype
MGI:3785402

cx11

• Allelic Composition: Flnb^Gt(XD076)Byg/Flnb^Gt(XD076)Byg; Runx2^tm1Mjo/Runx2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

skeleton

skeleton phenotype ( J:134094 )

N • mice exhibit normal cervical vertebrae

wide cranial sutures ( J:134094 )

• at P0, cranial sutures remain open

small occipital bone ( J:134094 )

• at P0, the occipital bone is less developed than in Runx2^tm1Mjo heterozygotes

abnormal sternebra morphology ( J:134094 )

• ossification between sternebrae observed in Flnb^Gt(XD076)Byg homozygotes is partially rescued

craniofacial

wide cranial sutures ( J:134094 )

• at P0, cranial sutures remain open

small occipital bone ( J:134094 )

• at P0, the occipital bone is less developed than in Runx2^tm1Mjo heterozygotes

Genotype
MGI:5689554

cx12

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Runx3^tm1Yg/Runx3^tm1Yg
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

mortality/aging

postnatal lethality, incomplete penetrance ( J:224290 )

• only a few mice survive to 1 week of age

skeleton

delayed bone ossification ( J:224290 )

• digital bones of 0.5 day old mice remain grossly cartilaginous indicating delayed skeletal ossification

Genotype
MGI:3582296

cx13

• Allelic Composition: Tle5^tm1Grid/Tle5^tm1Grid; Runx2^tm1Mjo/Runx2⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

skeleton

clavicle hypoplasia ( J:92187 )

• these mutants possess hypoplastic clavicles with no medial cartilaginous anlage, similar to the phenotype observed in Runx2 heterozygotes

decreased bone mineral density ( J:92187 )

• at 1 week after birth, these mutants display a phenotype of osteopenia, which worsens at 2-4 weeks after birth

abnormal skeleton development ( J:92187 )

• these mutants show reduced skeletal development and growth relative to control littermates

abnormal fontanelle morphology ( J:92187 )

• these mutants exhibit a more severe defect in fontanelle closure relative to heterozygous Runx2 mice

abnormal long bone hypertrophic chondrocyte zone ( J:92187 )

• these mutants show expansion of the resting zone and thinner zones of proliferation and hypertrophy in the growth plate relative to control littermates

decreased width of hypertrophic chondrocyte zone ( J:92187 )

• the growth plates of the tibia and humerus show reduced thickness due to a reduction in the thickness of the proliferative as well as the hypertrophic zones

decreased long bone epiphyseal plate size ( J:92187 )

• these mutants show an exacerbated reduction in the overall height of growth plates of the tibia and humerus, and in the amount of trabecular bone subjacent to the growth plates relative to Aes homozygous null littermates

• this severe growth plate defect is largely attributed to reduced Ihh signaling

growth/size/body

decreased body weight ( J:92187 )

• 80% of these mutants display body weights in the range of 28-75% of control wild-type or Aes heterozygous null littermates

• the weights of ~20% of these mice are less than 50% the weight of wild-type littermates; the weights of ~30% are between 50% and 60% of wild-type weights

• no sex differences are noted during the first 5 weeks of postnatal growth; however, subsequently the weight differences between female mutant and wild-type mice are not as large as they are in males

disproportionate dwarf ( J:92187 )

• at 1 week after birth, these mutants display a phenotype of dwarfism, which progressively worsens at 2-4 weeks after birth

• although mutants recover to some extent after 5 weeks of age, they remain consistently smaller than their littermates

postnatal growth retardation ( J:92187 )

• these mutants exhibit significant individual variation in the severity of the growth defect

• males are severely affected and remain small up to 6 months of age; in contrast, the weight and size of female mutants approach wild-type values after 2-3 months of age

craniofacial

abnormal fontanelle morphology ( J:92187 )

• these mutants exhibit a more severe defect in fontanelle closure relative to heterozygous Runx2 mice

reproductive system

female infertility ( J:92187 )

♀ • the cause of female infertility requires further investigation

male infertility ( J:92187 )

♂ • the cause of male infertility requires further investigation

Genotype
MGI:3582479

cx14

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Twist1^tm1Bhr/Twist1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

craniofacial

craniofacial phenotype ( J:90056 )

N • in contrast to the craniosynostotic Twist1^tm1Bhr heterozygotes, 10-day-old mice doubly heterozygous for Runx2^tm1Mjo and Twist1^tm1Bhr exhibit a normally shaped skull, intraparietal bones of nearly normal size, and no premature fusion of coronal sutures

skeleton

clavicle hypoplasia ( J:90056 )

• notably, 10-day-old mice doubly heterozygotes for Runx2^tm1Mjo and Twist1^tm1Bhr continue to display the clavicle hypoplasia of Runx2^tm1Mjo heterozygotes

Genotype
MGI:3582480

cx15

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Twist2^tm1(cre)Dor/Twist2^tm1(cre)Dor
• Genetic Background: involves: 129X1/SvJ * C57BL/6

skeleton

skeleton phenotype ( J:90056 )

N • newborns heterozygous for Runx2^tm1Mjo and homozygotes for Twist2^tm1Dor exhibit an almost complete rescue of the clavicle hypoplasia characteristic of Runx2^tm1Mjo heterozygotes

small interparietal bone ( J:90056 )

• similar to Runx2^tm1Mjo heterozygotes, newborns heterozygous for Runx2^tm1Mjo and homozygotes for Twist2^tm1Dor exhibit a reduction in the size of the intraparietal bone

delayed fontanelle closure ( J:90056 )

• similar to Runx2^tm1Mjo heterozygotes, newborns heterozygous for Runx2^tm1Mjo and homozygotes for Twist2^tm1Dor display a delay in closure of the fontanelles

craniofacial

small interparietal bone ( J:90056 )

• similar to Runx2^tm1Mjo heterozygotes, newborns heterozygous for Runx2^tm1Mjo and homozygotes for Twist2^tm1Dor exhibit a reduction in the size of the intraparietal bone

Genotype
MGI:3582481

cx16

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Twist2^tm1(cre)Dor/Twist2⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6

skeleton

clavicle hypoplasia ( J:90056 )

• similar to Runx2^tm1Mjo heterozygotes, newborn mice doubly heterozygous for Runx2^tm1Mjo and Twist2^tm1Dor display hypoplastic clavicles

Genotype
MGI:5550514

cx17

• Allelic Composition: Hivep3^tm1Glm/Hivep3^tm1Glm; Runx2^tm1Mjo/Runx2⁺
• Genetic Background: involves: C57BL/6

Trabecular bone and clavicle analysis in various mice with Runx2^tm1Mjo and/or Hivep3^tm1Glm alleles

skeleton

clavicle hypoplasia ( J:201597 )

Genotype
MGI:4887973

cx18

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Tg(Eno2tTA)#Nes/0; Tg(tetO-Zfp521)#Rbar/0
• Genetic Background: involves: C57BL/6 * SJL

skeleton

abnormal fontanelle morphology ( J:167992 )

• at P25, mice exhibit a defined nonmineralization area between the anterior and posterior fontanelles compared to in wild-type mice that is larger than in Runx2^tm1Mjo heterozygotes

abnormal hyoid bone morphology ( J:167992 )

• the midportion of the hyoid bone fails to mineralize unlike in wild-type mice

clavicle hypoplasia ( J:167992 )

• to a greater extent than in Runx2^tm1Mjo heterozygotes

craniofacial

abnormal fontanelle morphology ( J:167992 )

• at P25, mice exhibit a defined nonmineralization area between the anterior and posterior fontanelles compared to in wild-type mice that is larger than in Runx2^tm1Mjo heterozygotes

abnormal hyoid bone morphology ( J:167992 )

• the midportion of the hyoid bone fails to mineralize unlike in wild-type mice

Genotype
MGI:3696662

cx19

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Satb2^tm1Rug/Satb2⁺
• Genetic Background: Not Specified

skeleton

abnormal bone structure ( J:115876 )

decreased bone volume ( J:115876 )

• bone volume/total volume is reduced from 15.5% in wild-type to 3.53% in mutants

decreased bone trabecula number ( J:115876 )

• trabecular numbers/mm are reduced from 4.54 in wild-type to 0.79 in mutants

abnormal bone ossification ( J:115876 )

• display a marked reduction of bone formation at E15.5

Genotype
MGI:4887971

cx20

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Zfp521^tm2Ngc/Zfp521⁺
• Genetic Background: Not Specified

craniofacial

decreased hyoid bone size ( J:167992 )

• the mineralized midpoint of the hyoid bone is decreased in length compared to in wild-type mice

• however, mineralization occurs unlike in Runx2^tm1Mjo heterozygotes

skeleton

decreased hyoid bone size ( J:167992 )

• the mineralized midpoint of the hyoid bone is decreased in length compared to in wild-type mice

• however, mineralization occurs unlike in Runx2^tm1Mjo heterozygotes

clavicle hypoplasia ( J:167992 )

• clavicle is smaller than in wild-type mice but not as severely reduced as in Runx2^tm1Mjo heterozygotes