Mouse Genome Informatics
hm1
    Pitx2tm1Sac/Pitx2tm1Sac
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
• the number of fully differentiated hormone producing cells is decreased differentially along the dorsoventral axis
• the deficiency of Gnrhr, Lhb, and Fshb suggests a deficiency of gonadotropes
• expression of Gh and Ghrhr is reduced suggesting there are fewer fully differentiated somatotropes
• expression of Tshb is reduced suggesting there are fewer fully differentiated thyrotropes

homeostasis/metabolism
• at P1, expression of Fshb is nearly absent in the pituitary
• at P1, expression of Lhb is nearly absent in the pituitary

nervous system
• the number of fully differentiated hormone producing cells is decreased differentially along the dorsoventral axis
• the deficiency of Gnrhr, Lhb, and Fshb suggests a deficiency of gonadotropes
• expression of Gh and Ghrhr is reduced suggesting there are fewer fully differentiated somatotropes
• expression of Tshb is reduced suggesting there are fewer fully differentiated thyrotropes


Mouse Genome Informatics
hm2
    Pitx2tm1Sac/Pitx2tm1Sac
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
• embryos begin to die around E10.5 and only 1 of 41 was alive at E18.5

cardiovascular system
• heart position is biased towards the right possibly as a result of increased left lung size as initial looping is normal

growth/size

vision/eye
• eye muscles develop but are smaller than normal

endocrine/exocrine glands
N
• at E16.5 and E18.5 pituitary gland morphology appears normal (J:51160)

respiratory system

muscle
• eye muscles develop but are smaller than normal


Mouse Genome Informatics
ht3
    Pitx2tm1Sac/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
• in 2 of about 30 heterozygotes small eyes are seen

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

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

growth/size
• in 2 of about 30 heterozygotes mal-occluded incisors are seen
• in 2 of about 30 heterozygotes body size is reduced to 1/3 that of wild-type

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


Mouse Genome Informatics
ht4
    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
cn5
    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
N
• unlike Pitx2 null mice, growth rates and weights are normal (J:142726)


Mouse Genome Informatics
cx6
    Pitx1tm1Jdr/Pitx1tm1Jdr
Pitx2tm1Sac/Pitx2tm1Sac

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• in about 60% of comparisons limb bud reduction is greater in double homozygotes than in single homozygotes
• in about 50% of mutants the reduction in limb bud size is greater on the right side than on the left
• limb bud reduction is the result of narrowing of the limb bud so that it is only about 2 somites in length rather than 3.5/4 somites as in wild-type embryos apparently the result of a loss of anterior bud mesenchyme
• digit one is lost; however, the autopod is otherwise normal
• progressive loss of hindlimb skeletal elements is seen in a gene dosage dependent manner with loss of the right digit 1 being most sensitive followed by the right tibia then right femur, a similar pattern is seen on the left side
• the right and left femurs are absent
• identification of the fibula is based on contact with the calcaneus

skeleton
• the right and left femurs are absent
• identification of the fibula is based on contact with the calcaneus

endocrine/exocrine glands
• Rathke's pouch fails to expand normally at E12.5; however pituitary size is normal in either single homozygote

nervous system
• Rathke's pouch fails to expand normally at E12.5; however pituitary size is normal in either single homozygote

embryogenesis
• in about 60% of comparisons limb bud reduction is greater in double homozygotes than in single homozygotes
• in about 50% of mutants the reduction in limb bud size is greater on the right side than on the left
• limb bud reduction is the result of narrowing of the limb bud so that it is only about 2 somites in length rather than 3.5/4 somites as in wild-type embryos apparently the result of a loss of anterior bud mesenchyme


Mouse Genome Informatics
cx7
    Pitx1tm1Jdr/Pitx1tm1Jdr
Pitx2tm1Sac/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
endocrine/exocrine glands
• an intermediate reduction in the size of Rathke's pouch is seen compared to the double homozygote

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


Mouse Genome Informatics
cx8
    Pitx1tm1Jdr/Pitx1+
Pitx2tm1Sac/Pitx2tm1Sac

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 compared to the double homozygote

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


Mouse Genome Informatics
cx9
    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