Phenotypes associated with this allele

• Allele Symbol: Pitx2⁺
• Allele Name: wild type
• Allele ID: MGI:1857845
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Pitx2^tm1b(EUCOMM)Wtsi/Pitx2^+	C57BL/6N-Pitx2^tm1b(EUCOMM)Wtsi/H	MGI:5767763
ht2	Pitx2^tm1Sac/Pitx2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:2170004
ht3	Pitx2^tm2Sac/Pitx2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3589210
ht4	Pitx2^tm1Jfm/Pitx2^+	involves: 129S4/SvJaeSor	MGI:2172410
ht5	Pitx2^tm3Jfm/Pitx2^+	involves: 129S4/SvJaeSor * C57BL/6J	MGI:3776526
ht6	Pitx2^tm4(cre)Jfm/Pitx2^+	Not Specified	MGI:6315242
cn7	Irf6^tm1Bcsl/Irf6^tm1Bcsl Pitx2^tm4(cre)Jfm/Pitx2^+	involves: 129	MGI:6315241
cn8	Lmx1b^tm1Rjo/Lmx1b^tm4.1Rjo Pitx2^tm4(cre)Jfm/Pitx2^+	involves: 129S7/SvEvBrd	MGI:4818572
cx9	Pitx1^tm1Jdr/Pitx1^tm1Jdr Pitx2^tm2Sac/Pitx2^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5298059
cx10	Pitx1^tm1Jdr/Pitx1^tm1Jdr Pitx2^tm1Sac/Pitx2^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3589451
cx11	Pitx2^tm2Sac/Pitx2^+ Tbx1^tm1Bem/Tbx1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL	MGI:3690085

Genotype
MGI:5767763

ht1

• Allelic Composition: Pitx2^{tm1b(EUCOMM)Wtsi}/Pitx2⁺
• Genetic Background: C57BL/6N-Pitx2^{tm1b(EUCOMM)Wtsi}/H
• Cell Lines: EPD0688_3_A07

Data Sources

IMPC Data for Pitx2

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

behavior/neurological

increased grip strength ( J:211773 )

♀

IMPC - HAR

cardiovascular system

enlarged heart ( J:211773 )

♀

IMPC - HAR

craniofacial

abnormal tooth morphology ( J:211773 )

♂

IMPC - HAR

endocrine/exocrine glands

small testis ( J:211773 )

♂

IMPC - HAR

growth/size/body

enlarged heart ( J:211773 )

♀

IMPC - HAR

abnormal tooth morphology ( J:211773 )

♂

IMPC - HAR

nervous system

abnormal optic disk morphology ( J:211773 )

♀

IMPC - HAR

reproductive system

small testis ( J:211773 )

♂

IMPC - HAR

skeleton

abnormal tooth morphology ( J:211773 )

♂

IMPC - HAR

vision/eye

abnormal optic disk morphology ( J:211773 )

♀

IMPC - HAR

irregularly shaped pupil ( J:211773 )

IMPC - HAR

cornea opacity ( J:211773 )

IMPC - HAR

Genotype
MGI:2170004

ht2

• Allelic Composition: Pitx2^tm1Sac/Pitx2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

vision/eye

abnormal pupil morphology ( J:51160 )

• multiple pupillary openings are seen in about 10% of heterozygotes

abnormal placement of pupils ( J:51160 )

• seen in about 10% of heterozygotes

anisocoria ( J:51160 )

• seen in about 10% of heterozygotes

cataract ( J:51160 )

• clouded lenses are seen in about 10% of heterozygotes

microphthalmia ( J:51160 )

• in 2 of about 30 heterozygotes small eyes are seen

craniofacial

misaligned incisors ( J:51160 )

• in 2 of about 30 heterozygotes mal-occluded incisors are seen

malocclusion ( J:51160 )

• in 2 of about 30 heterozygotes mal-occluded incisors are seen

skeleton

misaligned incisors ( J:51160 )

• in 2 of about 30 heterozygotes mal-occluded incisors are seen

malocclusion ( J:51160 )

• in 2 of about 30 heterozygotes mal-occluded incisors are seen

growth/size/body

misaligned incisors ( J:51160 )

• in 2 of about 30 heterozygotes mal-occluded incisors are seen

malocclusion ( J:51160 )

• in 2 of about 30 heterozygotes mal-occluded incisors are seen

decreased body size ( J:51160 )

• in 2 of about 30 heterozygotes body size is reduced to 1/3 that of wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Axenfeld-Rieger syndrome type 1		DOID:0110120	OMIM:180500	J:51160

Genotype
MGI:3589210

ht3

• Allelic Composition: Pitx2^tm2Sac/Pitx2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

vision/eye

abnormal pupil morphology ( J:51160 )

• multiple pupillary openings are seen in about 10% of heterozygotes

abnormal placement of pupils ( J:51160 )

• seen in about 10% of heterozygotes

anisocoria ( J:51160 )

• seen in about 10% of heterozygotes

cataract ( J:51160 )

• clouded lenses are seen in about 10% of heterozygotes

microphthalmia ( J:51160 )

• 2 of about 30 have small eyes

craniofacial

misaligned incisors ( J:51160 )

• 2 of about 30 have mal-occluded incisors

malocclusion ( J:51160 )

• 2 of about 30 have mal-occluded incisors

skeleton

misaligned incisors ( J:51160 )

• 2 of about 30 have mal-occluded incisors

malocclusion ( J:51160 )

• 2 of about 30 have mal-occluded incisors

growth/size/body

misaligned incisors ( J:51160 )

• 2 of about 30 have mal-occluded incisors

malocclusion ( J:51160 )

• 2 of about 30 have mal-occluded incisors

decreased body size ( J:51160 )

• 2 of about 30 are about 1/3 the size of wild-type males

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Axenfeld-Rieger syndrome type 1		DOID:0110120	OMIM:180500	J:51160

Genotype
MGI:2172410

ht4

• Allelic Composition: Pitx2^tm1Jfm/Pitx2⁺
• Genetic Background: involves: 129S4/SvJaeSor

respiratory system

right pulmonary isomerism ( J:69854 )

• about 25% of adult heterozygotes display partial right pulmonary isomerism with an extra fissure at the cranial aspect of the left lung

cardiovascular system

irregular heartbeat ( J:160540 )

• more frequent occurrence of burst pacing induced atrial arrhythmias

• in the absence of stimulus no signs of atrial arrhythmia are detected

atrial fibrillation ( J:160540 )

• more frequent occurrence of burst pacing induced atrial fibrillations

• in the absence of stimulus no signs of atrial fibrillation are detected

prolonged QRS complex duration ( J:160540 )

• slight but significant prolongation of the QRS interval under baseline conditions

digestive/alimentary system

digestive/alimentary phenotype ( J:69854 )

N • rotation of the duodenum is normal

growth/size/body

right pulmonary isomerism ( J:69854 )

• about 25% of adult heterozygotes display partial right pulmonary isomerism with an extra fissure at the cranial aspect of the left lung

Genotype
MGI:3776526

ht5

• Allelic Composition: Pitx2^tm3Jfm/Pitx2⁺
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:79853 )

• animals are viable; no phenotypic details given

Genotype
MGI:6315242

ht6

• Allelic Composition: Pitx2^tm4(cre)Jfm/Pitx2⁺
• Genetic Background: Not Specified

craniofacial

abnormal enamel morphology ( J:275989 )

• mild enamel hypoplasia

growth/size/body

abnormal enamel morphology ( J:275989 )

• mild enamel hypoplasia

skeleton

abnormal enamel morphology ( J:275989 )

• mild enamel hypoplasia

Genotype
MGI:6315241

cn7

• Allelic Composition: Irf6^tm1Bcsl/Irf6^tm1Bcsl; Pitx2^tm4(cre)Jfm/Pitx2⁺
• Genetic Background: involves: 129

craniofacial

abnormal tooth morphology ( J:275989 )

• total tooth volume is reduced for upper incisors, upper first molars, and lower first molars at P28

abnormal incisor morphology ( J:275989 )

• incisors are variably hypoplastic with pitted labial surfaces at P14 but not at birth

• at P28, incisors continue to exhibit disrupted ameloblast polarity, reduced enamel space, and persistence of immature enamel matrix

abnormal incisor color ( J:275989 )

• by P28, enamel is whiter and more translucent

abnormal molar morphology ( J:275989 )

• molars exhibit increased attrition following eruption such that in some mice by 7 days posteruption (P28), crown wear reaches the dentin in first molars and by P84, molar cusps are worn almost completely flat

taurodontia ( J:275989 )

• root patterning defects include severely taurodontic mandibular second molars

abnormal molar crown morphology ( J:275989 )

• mice exhibit defects in molar crown morphology

• crown anomalies are more evident posteruption (P28 and P84)

abnormal molar cusp morphology ( J:275989 )

• at preeruption strages of P7 and P14, molar cusps are shallower in appearance

• 25% of mice show complete loss of cusp patterning

abnormal molar root morphology ( J:275989 )

• root patterning defects that include severely taurodontic (enlarged pulp chambers, apical displacement of the pulpal floor, reduced separation or fusion of mesial and distal roots, and reduced constriction at the cementum-enamel junction) mandibular second molars and peg-shaped mandibular first molar roots

• C-shaped roots in mandibular second molars

• single canal in single-rooted mandibular first molars

decreased molar number ( J:275989 )

• 3 mice have missing mandibular third molars unilaterally and 1 is missing a maxillary third molar

abnormal enamel morphology ( J:275989 )

• the enamel matrix layer is reduced

abnormal enamel development ( J:275989 )

• P28 mice exhibit a more radiolucent enamel layer in immature stages of amelogenesis and a more incisally located transition from immature to mature enamel indicating delayed enamel maturation

abnormal ameloblast morphology ( J:275989 )

• aberrant ameloblast organization and function

• the ameloblast layer appears ragged and discontinuous at P7

• molar ameloblasts appear less organized, with increased space between cells at P14

• ameloblasts appear to persist in the secretory stage as compared with the shorter mature ameloblasts in incisors

abnormal enamel mineralization ( J:275989 )

• mandibular molars exhibit decreased enamel mineral density prior to eruption (P14)

• however, at posteruption stages, the enamel mineral density recovers to levels seen in heterozygous Cre mice but is still less than in wild-type controls

• however, dentin density, percentage dentin volume, and percentage enamel volume are normal

abnormal enamel rod pattern ( J:275989 )

• shearing of enamel rods is seen in P28 mice

reduced enamel thickness ( J:275989 )

• mice exhibit thinner mandibular incisor enamel, particularly at P14

supernumerary teeth ( J:275989 )

• two mice have supernumerary teeth, one with an extra mandibular incisor and one with a diastema tooth

abnormal Hertwig epithelial root sheath morphology ( J:275989 )

• epithelial morphology is perturbed in Hertwigs epithelial root sheath, which appears shortened

growth/size/body

abnormal tooth morphology ( J:275989 )

• total tooth volume is reduced for upper incisors, upper first molars, and lower first molars at P28

abnormal incisor morphology ( J:275989 )

• incisors are variably hypoplastic with pitted labial surfaces at P14 but not at birth

• at P28, incisors continue to exhibit disrupted ameloblast polarity, reduced enamel space, and persistence of immature enamel matrix

abnormal incisor color ( J:275989 )

• by P28, enamel is whiter and more translucent

abnormal molar morphology ( J:275989 )

• molars exhibit increased attrition following eruption such that in some mice by 7 days posteruption (P28), crown wear reaches the dentin in first molars and by P84, molar cusps are worn almost completely flat

taurodontia ( J:275989 )

• root patterning defects include severely taurodontic mandibular second molars

abnormal molar crown morphology ( J:275989 )

• mice exhibit defects in molar crown morphology

• crown anomalies are more evident posteruption (P28 and P84)

abnormal molar cusp morphology ( J:275989 )

• at preeruption strages of P7 and P14, molar cusps are shallower in appearance

• 25% of mice show complete loss of cusp patterning

abnormal molar root morphology ( J:275989 )

• root patterning defects that include severely taurodontic (enlarged pulp chambers, apical displacement of the pulpal floor, reduced separation or fusion of mesial and distal roots, and reduced constriction at the cementum-enamel junction) mandibular second molars and peg-shaped mandibular first molar roots

• C-shaped roots in mandibular second molars

• single canal in single-rooted mandibular first molars

decreased molar number ( J:275989 )

• 3 mice have missing mandibular third molars unilaterally and 1 is missing a maxillary third molar

abnormal enamel morphology ( J:275989 )

• the enamel matrix layer is reduced

abnormal enamel development ( J:275989 )

• P28 mice exhibit a more radiolucent enamel layer in immature stages of amelogenesis and a more incisally located transition from immature to mature enamel indicating delayed enamel maturation

abnormal ameloblast morphology ( J:275989 )

• aberrant ameloblast organization and function

• the ameloblast layer appears ragged and discontinuous at P7

• molar ameloblasts appear less organized, with increased space between cells at P14

• ameloblasts appear to persist in the secretory stage as compared with the shorter mature ameloblasts in incisors

abnormal enamel mineralization ( J:275989 )

• mandibular molars exhibit decreased enamel mineral density prior to eruption (P14)

• however, at posteruption stages, the enamel mineral density recovers to levels seen in heterozygous Cre mice but is still less than in wild-type controls

• however, dentin density, percentage dentin volume, and percentage enamel volume are normal

abnormal enamel rod pattern ( J:275989 )

• shearing of enamel rods is seen in P28 mice

reduced enamel thickness ( J:275989 )

• mice exhibit thinner mandibular incisor enamel, particularly at P14

supernumerary teeth ( J:275989 )

• two mice have supernumerary teeth, one with an extra mandibular incisor and one with a diastema tooth

abnormal Hertwig epithelial root sheath morphology ( J:275989 )

• epithelial morphology is perturbed in Hertwigs epithelial root sheath, which appears shortened

skeleton

abnormal tooth morphology ( J:275989 )

• total tooth volume is reduced for upper incisors, upper first molars, and lower first molars at P28

abnormal incisor morphology ( J:275989 )

• incisors are variably hypoplastic with pitted labial surfaces at P14 but not at birth

• at P28, incisors continue to exhibit disrupted ameloblast polarity, reduced enamel space, and persistence of immature enamel matrix

abnormal incisor color ( J:275989 )

• by P28, enamel is whiter and more translucent

abnormal molar morphology ( J:275989 )

• molars exhibit increased attrition following eruption such that in some mice by 7 days posteruption (P28), crown wear reaches the dentin in first molars and by P84, molar cusps are worn almost completely flat

taurodontia ( J:275989 )

• root patterning defects include severely taurodontic mandibular second molars

abnormal molar crown morphology ( J:275989 )

• mice exhibit defects in molar crown morphology

• crown anomalies are more evident posteruption (P28 and P84)

abnormal molar cusp morphology ( J:275989 )

• at preeruption strages of P7 and P14, molar cusps are shallower in appearance

• 25% of mice show complete loss of cusp patterning

abnormal molar root morphology ( J:275989 )

• root patterning defects that include severely taurodontic (enlarged pulp chambers, apical displacement of the pulpal floor, reduced separation or fusion of mesial and distal roots, and reduced constriction at the cementum-enamel junction) mandibular second molars and peg-shaped mandibular first molar roots

• C-shaped roots in mandibular second molars

• single canal in single-rooted mandibular first molars

decreased molar number ( J:275989 )

• 3 mice have missing mandibular third molars unilaterally and 1 is missing a maxillary third molar

abnormal enamel morphology ( J:275989 )

• the enamel matrix layer is reduced

abnormal enamel development ( J:275989 )

• P28 mice exhibit a more radiolucent enamel layer in immature stages of amelogenesis and a more incisally located transition from immature to mature enamel indicating delayed enamel maturation

abnormal ameloblast morphology ( J:275989 )

• aberrant ameloblast organization and function

• the ameloblast layer appears ragged and discontinuous at P7

• molar ameloblasts appear less organized, with increased space between cells at P14

• ameloblasts appear to persist in the secretory stage as compared with the shorter mature ameloblasts in incisors

abnormal enamel mineralization ( J:275989 )

• mandibular molars exhibit decreased enamel mineral density prior to eruption (P14)

• however, at posteruption stages, the enamel mineral density recovers to levels seen in heterozygous Cre mice but is still less than in wild-type controls

• however, dentin density, percentage dentin volume, and percentage enamel volume are normal

abnormal enamel rod pattern ( J:275989 )

• shearing of enamel rods is seen in P28 mice

reduced enamel thickness ( J:275989 )

• mice exhibit thinner mandibular incisor enamel, particularly at P14

supernumerary teeth ( J:275989 )

• two mice have supernumerary teeth, one with an extra mandibular incisor and one with a diastema tooth

abnormal Hertwig epithelial root sheath morphology ( J:275989 )

• epithelial morphology is perturbed in Hertwigs epithelial root sheath, which appears shortened

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cleft lip		DOID:9296		J:275989

Genotype
MGI:4818572

cn8

• Allelic Composition: Lmx1b^tm1Rjo/Lmx1b^tm4.1Rjo; Pitx2^tm4(cre)Jfm/Pitx2⁺
• Genetic Background: involves: 129S7/SvEvBrd

vision/eye

abnormal intraocular muscle morphology ( J:161793 )

• expression analysis indicates the absence of sphincter and dilator muscles in the iris

abnormal iridocorneal angle ( J:161793 )

• angle closure

absent trabecular meshwork ( J:161793 )

absent ciliary body ( J:161793 )

• not detectable

irregularly shaped pupil ( J:161793 )

• at P13

iris hypoplasia ( J:161793 )

abnormal cornea morphology ( J:161793 )

abnormal cornea endothelium morphology ( J:161793 )

• decrease in the amount of corneal endothelial tissue

cornea opacity ( J:161793 )

• at P13

abnormal lens morphology ( J:161793 )

abnormal lens epithelium morphology ( J:161793 )

• thickened

small lens ( J:161793 )

• about 20% smaller relative to overall eye size

microphthalmia ( J:161793 )

• in about 25% of mice at 3 weeks of age

muscle

abnormal intraocular muscle morphology ( J:161793 )

• expression analysis indicates the absence of sphincter and dilator muscles in the iris

Genotype
MGI:5298059

cx9

• Allelic Composition: Pitx1^tm1Jdr/Pitx1^tm1Jdr; Pitx2^tm2Sac/Pitx2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

embryo

small hindlimb buds ( J:80020 )

• reduced hindlimb bud

• extends across 2 somites centering on somite 27

limbs/digits/tail

small hindlimb buds ( J:80020 )

• reduced hindlimb bud

• extends across 2 somites centering on somite 27

absent femur ( J:80020 )

• failure of stylopod (femur) development

skeleton

absent femur ( J:80020 )

• failure of stylopod (femur) development

Genotype
MGI:3589451

cx10

• Allelic Composition: Pitx1^tm1Jdr/Pitx1^tm1Jdr; Pitx2^tm1Sac/Pitx2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

endocrine/exocrine glands

small Rathke's pouch ( J:73774 )

• an intermediate reduction in the size of Rathke's pouch is seen compared to the double homozygote

nervous system

small Rathke's pouch ( J:73774 )

• an intermediate reduction in the size of Rathke's pouch is seen compared to the double homozygote

Genotype
MGI:3690085

cx11

• Allelic Composition: Pitx2^tm2Sac/Pitx2⁺; Tbx1^tm1Bem/Tbx1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:107397 )

• become cyanotic immediately after birth and die

cardiovascular system

supravalvar pulmonary trunk stenosis ( J:107397 )

• stenosis of the pulmonary trunk

abnormal heart morphology ( J:107397 )

• exhibit severe cardiac defects with incomplete penetrance (about 60%) at E15.5, E18.5 and in newborns

abnormal fetal atrioventricular canal morphology ( J:107397 )

• enlarged atrioventricular canal at E10.5

abnormal coronary vessel morphology ( J:107397 )

• occasionally see malformation of the coronary vessels

abnormal heart and great vessel attachment ( J:107397 )

• occasionally see mispositioning of the aorta

double outlet right ventricle ( J:107397 )

• some show the aorta and the pulmonary artery arising from the right ventricle

anomalous pulmonary venous connection ( J:107397 )

• abnormal drainage of the pulmonary vein into a common instead of the left atrium

abnormal atrioventricular valve morphology ( J:107397 )

• atrioventricular valve defects

common atrioventricular valve ( J:107397 )

atrial septal defect ( J:107397 )

• atrial septal defects

abnormal heart shape ( J:107397 )

• hearts are malformed, however they are properly patterned in the atrioventricular canal and around the inner curvature

abnormal heart ventricle morphology ( J:107397 )

• reduced ventricular expansion and abnormal ventricular shape are seen at E10.5

ventricular septal defect ( J:107397 )

• ventricular septal defects

homeostasis/metabolism

cyanosis ( J:107397 )

• become cyanotic immediately after birth