Mouse Genome Informatics
hm1
    Pitx2tm2Sac/Pitx2tm2Sac
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• profound anterior pituitary gland hypoplasia is seen; however the infundibulum appears normal

nervous system
• profound anterior pituitary gland hypoplasia is seen; however the infundibulum appears normal


Mouse Genome Informatics
hm2
    Pitx2tm2Sac/Pitx2tm2Sac
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

cardiovascular system
• the leaflets of the vena cava are defective
• the membranous portion of the valves is reduced
• at E12.5 and E13.5 only a single, hugely distended atrium is seen
• 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
• the ventricular septum is dysmorphic
• progressive enlargement of the heart is seen by E12.5

embryogenesis
• all homozygous embryos bend severely rightward rostral to the developing hindlimb
• embryos are moderately undersized at E12.5

endocrine/exocrine glands
• the mesenchymal layer surrounding Rathke's pouch is hypercellular
• 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
• 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)
• the pouch pinches off later in homozygotes and is markedly hypocellular at E12.5 (J:99227)

vision/eye
• the developing corneal epithelium is thicker than normal
• at E12.5, the eyes lie below the surface epithelium and are rotated so that the lens does not directly face the surface ectoderm
• at E12.5, the optic cup is separated from the surface ectoderm by an abnormally thick mesenchymal layer
• mesenchymal condensations that will develop into extrinsic eye muscles are absent at E12.5
• at E12.5, vestigal lens pits are still present in some eyes
• at E12.5, closure of the optic fissure is delayed or defective
• at E12.5 homozygous eyes are smaller than normal

nervous system
• 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
• the mesenchymal layer surrounding Rathke's pouch is hypercellular
• 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
• 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)
• the pouch pinches off later in homozygotes and is markedly hypocellular at E12.5 (J:99227)
• in about 5% of embryos the crown of the head is open over the midbrain

growth/size/body
• embryos are moderately undersized at E12.5
• 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

respiratory system

muscle
• mesenchymal condensations that will develop into extrinsic eye muscles are absent at E12.5

cellular
• 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


Mouse Genome Informatics
ht3
    Pitx2tm2Sac/Pitx2+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• multiple pupillary openings are seen in about 10% of heterozygotes
• seen in about 10% of heterozygotes
• seen in about 10% of heterozygotes
• clouded lenses are seen in about 10% of heterozygotes
• 2 of about 30 have small eyes

craniofacial
• 2 of about 30 have mal-occluded incisors
• 2 of about 30 have mal-occluded incisors

skeleton
• 2 of about 30 have mal-occluded incisors

growth/size/body
• 2 of about 30 have mal-occluded incisors
• 2 of about 30 are about 1/3 the size of wild-type males

Mouse Models of Human Disease
OMIM IDRef(s)
Axenfeld-Rieger Syndrome, Type 1; RIEG1 180500 J:51160


Mouse Genome Informatics
ht4
    Pitx2tm1.1Dmm/Pitx2tm2Sac
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• abdominal and abdominal viscera defects similar to in Pitx2tm2Sac homozygotes
• distal turning defect similar to in Pitx2tm2Sac homozygotes

nervous system
• mice lack migration of subthalamic neurons and recruitment of their projections into an expanded mammillotegmental tract
• mice lack migration of subthalamic neurons and recruitment of their projections into an expanded mammillotegmental tract

cardiovascular system
• similar to in Pitx2tm2Sac homozygotes

vision/eye
• medially displaced

craniofacial

cellular
• mice lack migration of subthalamic neurons and recruitment of their projections into an expanded mammillotegmental tract

endocrine/exocrine glands

growth/size/body


Mouse Genome Informatics
ht5
    Pitx2tm1Sac/Pitx2tm2Sac
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• 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

nervous system
• 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


Mouse Genome Informatics
cn6
    Pitx2tm1.1Sac/Pitx2tm2Sac
Tg(Wnt1-cre)11Rth/?
Gt(ROSA)26Sortm1Sor/?

involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• devoid of pigment except for a cone shaped region in the anterior segment
• retinal pigment layer is normal at E10.5 but pigment loss begins at E12.5
• corneal stroma and epithelium are absent
• hypomorphic hyaloid blood vessels
• muscle bundles present adjacent to the anterior segment
• 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
• 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

pigmentation
• devoid of pigment except for a cone shaped region in the anterior segment
• retinal pigment layer is normal at E10.5 but pigment loss begins at E12.5

nervous system

muscle
• muscle bundles present adjacent to the anterior segment


Mouse Genome Informatics
cn7
    Pitx2tm1.1Sac/Pitx2tm2Sac
Tg(Tshb-cre)1Sac/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• at 5 weeks, males and females have lower body weights than control littermates; female weight differences are greatest at 5 weeks, but are also lower at other post-weaning ages (weeks 4 through 8) while difference is smaller but still significant in males at 5 weeks

homeostasis/metabolism
N
• at 8 weeks, circulating thyroid-stimulating hormone (TSH) levels are not different in mutants and controls (J:197591)
• serum levels of total thyroxine (T4) are within normal ranges for male and female mutants (J:197591)
• following dietary-induced hypothyroidism for 4 weeks, mutants have a 48-fold increase in serum TSH levels, but this increase is inferior to the 80-fold increased serum TSH seen in controls fed the same low iodine diet for 4 weeks
• mutant thus show a blunted TSH response to hypothyroidism relative to controls

endocrine/exocrine glands
• thyroid gland volume is smaller in mutants than in controls; however, follicular size and height of follicular epithelia are indistinguishable from controls


Mouse Genome Informatics
cn8
    Pitx2tm1Sac/Pitx2tm2Sac
Tg(Lhb-cre)1Sac/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• unlike Pitx2 null mice, mice exhibit normal gonadal development, puberty and fertility (J:142726)

growth/size/body
N
• unlike Pitx2 null mice, growth rates and weights are normal (J:142726)


Mouse Genome Informatics
cx9
    Pitx1tm1Jdr/Pitx1tm1Jdr
Pitx2tm2Sac/Pitx2+

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• reduced hindlimb bud
• extends across 2 somites centering on somite 27

limbs/digits/tail
• reduced hindlimb bud
• extends across 2 somites centering on somite 27
• failure of stylopod (femur) development

skeleton
• failure of stylopod (femur) development


Mouse Genome Informatics
cx10
    Pitx1tm1Jdr/Pitx1tm1Jdr
Pitx2tm1Sac/Pitx2tm2Sac

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• both stylopod and autopod severely affected

limbs/digits/tail
• both stylopod and autopod severely affected


Mouse Genome Informatics
cx11
    Pitx2tm2Sac/Pitx2+
Tbx1tm1Bem/Tbx1+

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• become cyanotic immediately after birth and die

cardiovascular system
• stenosis of the pulmonary trunk
• exhibit severe cardiac defects with incomplete penetrance (about 60%) at E15.5, E18.5 and in newborns
• enlarged atrioventricular canal at E10.5
• occasionally see malformation of the coronary vessels
• occasionally see mispositioning of the aorta
• some show the aorta and the pulmonary artery arising from the right ventricle
• abnormal drainage of the pulmonary vein into a common instead of the left atrium
• atrioventricular valve defects
• atrial septal defects
• hearts are malformed, however they are properly patterned in the atrioventricular canal and around the inner curvature
• reduced ventricular expansion and abnormal ventricular shape are seen at E10.5
• ventricular septal defects

homeostasis/metabolism
• become cyanotic immediately after birth