Mouse Genome Informatics
hm1
    Pitx1tm1Jdr/Pitx1tm1Jdr
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
• limb bud size is reduced and in about 50% of mutants the reduction 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 2.5 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 on the right hindlimb is lost
• some hindlimb specific features are lost and replaced by features resembling the forelimb (for example diameter of the tibia and fibula and articulation of the knee joint)
• the femur directly contacts the fibula and is shorter than normal
• the reduction in femur length is often greater on the right side than on the left
• the diameters of the tibia and fibula are similar and the fibula directly contacts the femur
• the diameters of the tibia and fibula are similar

skeleton
• the femur directly contacts the fibula and is shorter than normal
• the reduction in femur length is often greater on the right side than on the left
• the diameters of the tibia and fibula are similar and the fibula directly contacts the femur
• the diameters of the tibia and fibula are similar
• attachment of the pelvic bones is often displaced posteriorly with attachment to the to the second or third sacral vertebra and this attachment is sometimes asymmetrical with greater displacement on the right than the left
• some homozygotes lack the ilium with attachment to the vertebrae through the acetabulum
• the secondary cartilage of the hindlimb knee joint does not form

embryogenesis
• limb bud size is reduced and in about 50% of mutants the reduction 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 2.5 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
hm2
    Pitx1tm1Jdr/Pitx1tm1Jdr
involves: 129S1/Sv * 129X1/SvJ * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes die at birth

limbs/digits/tail
• forelimbs are normal but hindlimbs are shorter than normal
• hindlimb structures affected are all on the dorsal side and proximal structures are more severely affected than distal structures
• the femur is shorter than normal and in 5 of 6 cases the right femur is more severely affected than the left
• endochondral bone is greatly diminished
• calcification of the tibia is severely reduced with narrower cortical bone and reduced trabecular bone
• the tibia is shorter and narrower and is comparable in size to the fibula
• the knee joints lack a distinct fabella
• the knee joints lack a distinct patella

skeleton
• seen at E14.5
• no evidence of the gonial bone can be found
• the femur is shorter than normal and in 5 of 6 cases the right femur is more severely affected than the left
• endochondral bone is greatly diminished
• calcification of the tibia is severely reduced with narrower cortical bone and reduced trabecular bone
• the tibia is shorter and narrower and is comparable in size to the fibula
• the knee joints lack a distinct fabella
• the knee joints lack a distinct patella
• the pelvic bones are attached to the first sacral vertebra through the acetabulum rather than the ilium and in 2 cases the attachment is asymmetrical between the second and third sacral vertebra
• the ilium is absent or consists only of cartilaginous remnants
• slightly smaller
• pubic bone is slightly smaller
• the cartilage of the distal femur and tibia heads is greatly reduced
• abnormal bone formation is seen around the Meckel's cartilage all the way up to the malleus
• at the distal end of the tibia the hypertrophic chondrocytes are enlarged and their layer is expanded; however less extracellular matrix is produced and almost no mineralization is seen
• at the proximal end of the tibia, undifferentiated chondrocytes, articular cartilage, secondary ossification centers, and pre-hypertrophied chondrocytes are almost absent
• at the distal end of the tibia the hypertrophic chondrocytes are enlarged and their layer is expanded

craniofacial
• seen at E14.5
• no evidence of the gonial bone can be found
• abnormal bone formation is seen around the Meckel's cartilage all the way up to the malleus
• at E14.5 the palatal shelves fail to elevate and fuse resulting in a deficiency in maxillary epithelium
• at E14.5 a bifurcate tongue is present

hearing/vestibular/ear
• no evidence of the gonial bone can be found
• the tympanic bone does not reach the Meckel's cartilage

digestive/alimentary system
• at E14.5 the palatal shelves fail to elevate and fuse resulting in a deficiency in maxillary epithelium
• at E14.5 a bifurcate tongue is present


Mouse Genome Informatics
cx3
    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
cx4
    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
cx5
    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
cx6
    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
cx7
    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