Mouse Genome Informatics
hm1
    Pitx2tm1Jfm/Pitx2tm1Jfm
involves: 129S4/SvJaeSor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some loss of homozygous embryos is seen initially at E14.5

embryogenesis
• turning arrests suspending the lower trunk to the right of the upper trunk and about 10% of homozygotes have delayed turning

cardiovascular system
• the left superior caval vein is absent at E11.5 and E12.5
• at E10.5 the atrioventricular canal is distorted dorsally and rightward
• at E12.5 the atrioventricular cushions have not fused and there is a common atrioventricular junction
• at E10.5 the outflow tract is distorted dorsally and rightward (J:57674)
• at E11.5 the outflow tract has a larger than normal lumen with symmetrical cushions (J:69854)
• at E12.5 the outflow tract cushions are poorly aligned, the distal portion of the outflow tract is not septated, and the arterial trunks are poorly aligned (J:69854)
• all homozygotes have defects in ventriculoarterial connections including double outlet right ventricle
• all homozygotes have defects in ventriculoarterial connections including double outlet right ventricle and some have a common atrioventricular channel
• at E11.5 the pulmonary vein is abnormally connected to the right sinus horn of the heart and venous valves are located on the right and left
• at E12.5 the pulmonary vein has exits to both the right and left side of the heart
• all homozygotes have defects in ventriculoarterial connections including double outlet right ventricle and some have a common atrioventricular channel
• at E11.5 the dorsal left atrium is more extensively trabeculated than the right atrium, opposite to what is seen in wild-type embryos
• at E11.5 the primary interatrial septum is just a stub and at E12.5 it is truncated
• the defects seen in the heart are similar to those in humans with right atrial isomerism
• at E12.5 the hears is in a ventral, left-sided location with the apex directed cranially and rightward

vision/eye
• absent extraocular muscles
• in place of a cornea homozygotes have undifferentiated mesenchymal cells
• the anterior eye chamber is absent

digestive/alimentary system
• the abdominal contents form ventrally, inferior to the heart and to the left of the body axis (J:57674)
• in about 72% of homozygotes rotation of the duodenum does not occur and in about 17% rotation is reversed (J:69854)

craniofacial
• the mandibular facial prominence is abnormal
• the maxillary facial prominence is abnormal
• variable deficiency of the Meckel's cartilage is seen
• mandibular teeth arrest as tooth buds and maxillary teeth arrest at the placode stage (J:57674)

immune system

respiratory system
• the lungs form ventrally, inferior to the heart and to the left of the body axis and at E12.5 right pulmonary isomerism is seen; however the stomach maintains its left-sided normal morphology (J:57674)
• evident at the primary lung bud stage (E9.0) and the left-sided branching pattern is identical to that of the right lung bud (J:69854)

muscle
• absent extraocular muscles

skeleton
• the mandibular facial prominence is abnormal
• the maxillary facial prominence is abnormal
• variable deficiency of the Meckel's cartilage is seen

hematopoietic system

growth/size
• the defects seen in the heart are similar to those in humans with right atrial isomerism
• at E10.5 in homozygotes in which turning is minimally affected a patent umbilical ring and evisceration of the abdominal contents are seen
• the lungs form ventrally, inferior to the heart and to the left of the body axis and at E12.5 right pulmonary isomerism is seen; however the stomach maintains its left-sided normal morphology (J:57674)
• evident at the primary lung bud stage (E9.0) and the left-sided branching pattern is identical to that of the right lung bud (J:69854)

Mouse Models of Human Disease
OMIM IDRef(s)
Axenfeld-Rieger Syndrome, Type 1; RIEG1 180500 J:57674 , J:87220


Mouse Genome Informatics
ht2
    Pitx2tm1Jfm/Pitx2+
involves: 129S4/SvJaeSor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• about 25% of adult heterozygotes display partial right pulmonary isomerism with an extra fissure at the cranial aspect of the left lung

cardiovascular system
• more frequent occurrence of burst pacing induced atrial arrhythmias
• in the absence of stimulus no signs of atrial arrhythmia are detected
• more frequent occurrence of burst pacing induced atrial fibrillations
• in the absence of stimulus no signs of atrial fibrillation are detected
• slight but significant prolongation of the QRS interval under baseline conditions

digestive/alimentary system
N
• rotation of the duodenum is normal (J:69854)

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


Mouse Genome Informatics
ht3
    Pitx2tm1Jfm/Pitx2tm4(cre)Jfm
involves: 129S4/SvJaeSor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• mutant daughter cells move aberrantly in a dorsal direction out of the oral ectoderm, fail to populate the nasal process, and contribute fewer cells to the oral cavity roof compared to wild-type mice


Mouse Genome Informatics
ht4
    Pitx2tm1Jfm/Pitx2tm2Jfm
involves: 129S4/SvJaeSor
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• molars arrest prior to cap formation

Mouse Models of Human Disease
OMIM IDRef(s)
Axenfeld-Rieger Syndrome, Type 1; RIEG1 180500 J:87220


Mouse Genome Informatics
ht5
    Pitx2tm1Jfm/Pitx2tm2Jfm
involves: 129S4/SvJaeSor * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• about 50% of mutant embryos die by E16.5

cardiovascular system
• trabeculation of the right and left atria are similar, unlike in wild-type embryos where more extensive trabeculation is seen in the right atrium

respiratory system
• the left-sided branching pattern is right isomerized

digestive/alimentary system
• in about 14% of mutants rotation of the duodenum does not occur and in about 36% rotation is reversed

growth/size
• the left-sided branching pattern is right isomerized


Mouse Genome Informatics
ht6
    Pitx2tm1Jfm/Pitx2tm2.1Jfm
involves: 129S4/SvJaeSor * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryo loss is first detected at E18.5

cardiovascular system
• trabeculation of the right and left atria are similar, unlike in wild-type embryos where more extensive trabeculation is seen in the right atrium

respiratory system
• the left-sided branching pattern is right isomerized

digestive/alimentary system
• in about 83% rotation of the duodenum is reversed and in the rest rotation is normal

growth/size
• the left-sided branching pattern is right isomerized