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hm1
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Pitx2tm2Sac/Pitx2tm2Sac
involves: 129S1/Sv * 129X1/SvJ |
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• profound anterior pituitary gland hypoplasia is seen; however the infundibulum appears normal
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• profound anterior pituitary gland hypoplasia is seen; however the infundibulum appears normal
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hm2
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Pitx2tm2Sac/Pitx2tm2Sac
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J |
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• the leaflets of the vena cava are defective
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• the membranous portion of the valves is reduced
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• at E12.5 and E13.5 only a single, hugely distended atrium is seen
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• at E12.5, the heart is displaced leftward and ventrally by a proliferating mass of mesoderm cells which combined with a fissure in the ventral body wall results in a final external position
• the orientation of the heart is off by 90 degrees
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• the ventricular septum is dysmorphic
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• progressive enlargement of the heart is seen by E12.5
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• all homozygous embryos bend severely rightward rostral to the developing hindlimb
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• embryos are moderately undersized at E12.5
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• the mesenchymal layer surrounding Rathke's pouch is hypercellular
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• growth and differentiation of Rathke's pouch is arrested by E12.5; however initial formation of the pouch at E10.5 is normal
(J:51160)
• at E10.5 increased cell death is seen in homozygous mutant pouches and apoptotoc cells extend from the oral ectoderm further dorsally into the invaginating pouch than in wild-type embryos
(J:99227)
• the pouch pinches off later in homozygotes and is markedly hypocellular at E12.5
(J:99227)
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• the developing corneal epithelium is thicker than normal
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• at E12.5, the eyes lie below the surface epithelium and are rotated so that the lens does not directly face the surface ectoderm and closure of the optic fissure is delayed or defective
• at E12.5, the optic cup is separated from the surface ectoderm by an abnormally thick mesenchymal layer
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• mesenchymal condensations that will develop into extrinsic eye muscles are absent at E12.5
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• at E12.5, vestigal lens pits are still present in some eyes
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• at E12.5 homozygous eyes are smaller than normal
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• at E13.5 fewer neurons in the developing mesencephalon or future superior colliculus are labeled by retrograde diI labeling suggesting impaired radial or tangential migration; however the number of cells in M phase is not different from wild-type
• by E13.5, 4 of 5 homozygotes fail to develop projections from the subthalamic nucleus to the tegmentum
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• the mesenchymal layer surrounding Rathke's pouch is hypercellular
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• growth and differentiation of Rathke's pouch is arrested by E12.5; however initial formation of the pouch at E10.5 is normal
(J:51160)
• at E10.5 increased cell death is seen in homozygous mutant pouches and apoptotoc cells extend from the oral ectoderm further dorsally into the invaginating pouch than in wild-type embryos
(J:99227)
• the pouch pinches off later in homozygotes and is markedly hypocellular at E12.5
(J:99227)
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• in about 5% of embryos the crown of the head is open over the midbrain
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• embryos are moderately undersized at E12.5
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• a large fissure in the ventral body wall results in the heart, liver, and other abdominal organs being external and displaced leftward and outward at E12.5
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• mesenchymal condensations that will develop into extrinsic eye muscles are absent at E12.5
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• at E13.5 fewer neurons in the developing mesencephalon or future superior colliculus are labeled by retrograde diI labeling suggesting impaired radial or tangential migration; however the number of cells in M phase is not different from wild-type
• by E13.5, 4 of 5 homozygotes fail to develop projections from the subthalamic nucleus to the tegmentum
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ht3
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Pitx2tm2Sac/Pitx2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J |
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• multiple pupillary openings are seen in about 10% of heterozygotes
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• seen in about 10% of heterozygotes
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• seen in about 10% of heterozygotes
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• 2 of about 30 have small eyes
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• 2 of about 30 have mal-occluded incisors
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• 2 of about 30 have mal-occluded incisors
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• 2 of about 30 have mal-occluded incisors
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• 2 of about 30 are about 1/3 the size of wild-type males
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Mouse Models of Human Disease |
OMIM ID | Ref(s) | |
| Axenfeld-Rieger Syndrome, Type 1; RIEG1 | 180500 | J:51160 | |
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ht4
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Pitx2tm1.1Dmm/Pitx2tm2Sac
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J |
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• abdominal and abdominal viscera defects similar to in Pitx2tm2Sac homozygotes
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• distal turning defect similar to in Pitx2tm2Sac homozygotes
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• mice lack migration of subthalamic neurons and recruitment of their projections into an expanded mammillotegmental tract
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• mice lack migration of subthalamic neurons and recruitment of their projections into an expanded mammillotegmental tract
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• similar to in Pitx2tm2Sac homozygotes
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• medially displaced
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• severe
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• mice lack migration of subthalamic neurons and recruitment of their projections into an expanded mammillotegmental tract
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ht5
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Pitx2tm1Sac/Pitx2tm2Sac
involves: 129S1/Sv * 129X1/SvJ |
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• an intermediate reduction in the size of Rathke's pouch is seen in compound heterozygotes compared to mice homozygous for Pitx2tm2Sac; however the infundibulum appears normal
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• an intermediate reduction in the size of Rathke's pouch is seen in compound heterozygotes compared to mice homozygous for Pitx2tm2Sac; however the infundibulum appears normal
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cn6
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Pitx2tm1.1Sac/Pitx2tm2Sac Tg(Wnt1-cre)11Rth/? Gt(ROSA)26Sortm1Sor/? involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * CBA |
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• devoid of pigment except for a cone shaped region in the anterior segment
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• retinal pigment layer is normal at E10.5 but pigment loss begins at E12.5
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• corneal stroma and epithelium are absent
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• hypomorphic hyaloid blood vessels
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• muscle bundles present adjacent to the anterior segment
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• eye stalk fails to extend at E12.5
• eyes directly attached to ventral diencephalon by E14.5
• retinal ganglion cell axons enter ventral thalamus and form an optic chiasma-like structure
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• eyes are not visible externally at E16.5
• eyes present but buried within the skull near the midline directly beneath the brain
• lens and retina present
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• devoid of pigment except for a cone shaped region in the anterior segment
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• retinal pigment layer is normal at E10.5 but pigment loss begins at E12.5
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• muscle bundles present adjacent to the anterior segment
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cn7
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Pitx2tm1Sac/Pitx2tm2Sac Tg(Lhb-cre)1Sac/0 involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL |
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| N |
• unlike Pitx2 null mice, mice exhibit normal gonadal development, puberty and fertility
(J:142726)
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| N |
• unlike Pitx2 null mice, growth rates and weights are normal
(J:142726)
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cx8
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Pitx1tm1Jdr/Pitx1tm1Jdr Pitx2tm2Sac/Pitx2+ involves: 129S1/Sv * 129X1/SvJ |
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• reduced hindlimb bud
• extends across 2 somites centering on somite 27
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• reduced hindlimb bud
• extends across 2 somites centering on somite 27
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• failure of stylopod (femur) development
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• failure of stylopod (femur) development
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cx9
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Pitx1tm1Jdr/Pitx1tm1Jdr Pitx2tm1Sac/Pitx2tm2Sac involves: 129S1/Sv * 129X1/SvJ |
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• both stylopod and autopod severely affected
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• both stylopod and autopod severely affected
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cx10
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Pitx2tm2Sac/Pitx2+ Tbx1tm1Bem/Tbx1+ involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL |
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• become cyanotic immediately after birth and die
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• stenosis of the pulmonary trunk
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• exhibit severe cardiac defects with incomplete penetrance (about 60%) at E15.5, E18.5 and in newborns
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• enlarged atrioventricular canal at E10.5
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• occasionally see malformation of the coronary vessels
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• occasionally see mispositioning of the aorta
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• some show the aorta and the pulmonary artery arising from the right ventricle
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• abnormal drainage of the pulmonary vein into a common instead of the left atrium
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• atrioventricular valve defects
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• atrial septal defects
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• hearts are malformed, however they are properly patterned in the atrioventricular canal and around the inner curvature
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• reduced ventricular expansion and abnormal ventricular shape are seen at E10.5
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• ventricular septal defects
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