Mouse Genome Informatics
hm1
    Tbx1tm1Bem/Tbx1tm1Bem
FVB.Cg-Tbx1tm1Bem
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 2 of 15 had a right sided aortic arch
• 15 of 15 had persistent truncus arteriosis

craniofacial
• 15 of 15 had an overt cleft palate

immune system
• a single lobe thyroid gland was present
• 15 of 15 had athymia

hematopoietic system
• a single lobe thyroid gland was present
• 15 of 15 had athymia

digestive/alimentary system
• 15 of 15 had an overt cleft palate

endocrine/exocrine glands
• a single lobe thyroid gland was present
• 15 of 15 had athymia

embryogenesis

muscle

hearing/vestibular/ear
• lack of defined inner ear structures
• missing middle ear structures

growth/size
• 15 of 15 had an overt cleft palate

Mouse Models of Human Disease
OMIM IDRef(s)
DiGeorge Syndrome; DGS 188400 J:91664
Velocardiofacial Syndrome 192430 J:91664


Mouse Genome Informatics
hm2
    Tbx1tm1Bem/Tbx1tm1Bem
involves: 129 * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• embryos show show a severe, single outflow vessel phenotype at E17.5


Mouse Genome Informatics
hm3
    Tbx1tm1Bem/Tbx1tm1Bem
involves: 129/Sv * C57BL/6J * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
• the otocyst is hypoplastic with impaired growth detected during placode invagination, around E9.0
• expression of genes normally seen in the anterior portion of the otocyst are suppressed and expression of posterior genes expanded posterolatterally
• identifiable vestibular and auditory sensory organs fail to form and at E13.5 the inner ear consists of 2 ventral chambers one of which appears to derive from the endolymphatic projection and has cuboidal epithelial cells like those in the wild-type endolymphatic duct

nervous system
• at E9.0 - E11 in the otic vesicle, ectopic neurogenesis is more widespread and persistent than in heterozygotes
• at E10 - E10.5 ectopic delamination and duplication of the cochlear ganglion rudiment is seen with the ganglion volume increased to 1.83-fold that of wild-type
• at E13.5 a secondary compound ganglion is seen apposed to and innervating the epithelial posterior pole and the central projection of the ganglion is absent
• at E14.5 the ganglia are necrotic and mostly absent at after E16.5

cellular
• at E9.0 - E11 in the otic vesicle, ectopic neurogenesis is more widespread and persistent than in heterozygotes


Mouse Genome Informatics
hm4
    Tbx1tm1Bem/Tbx1tm1Bem
involves: 129/Sv * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• absent in the caudal branchial region


Mouse Genome Informatics
ht5
    Tbx1tm1Bem/Tbx1+
B6.Cg-Tbx1tm1Bem
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mutants exhibit a higher degree of thigmotaxis in the inescapable open field than wild-type mice
• however, mutants are indistinguishable in anxiety-related behaviors in the elevated plus maze from wild-type mice
• mutants initially exhibit higher levels of contact with a novel, non-mouse object compared with wild-type mice
• mutants exhibit lower levels of spontaneous alternations in the T-maze at 0 and 30 second delays compared to wild-type mice; both wild-type and mutant mice reach a chance level at a 60 second delay
• in the T-maze, mutants visit the same arms across trials more often than wild-type mice when mutants show spontaneous alternation (0 second delay) but not when they do not show spontaneous alternation at a 60 second delay, indicating a repetitive behavioral tendency
• mutants exhibit lower levels of active and passive affiliative social interaction at 2 months of age, but no alterations in aggression, olfactory investigation or motor behavior
• mutant pups are impaired in complex patterns of vocalization but not simple vocal patterns
• pups exhibit vocalization less frequently in complex, two-syllable, composite, frequency steps and flat, and for shorter duration in harmonics, two-syllable, composite, and frequency steps

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:177772


Mouse Genome Informatics
ht6
    Tbx1tm1Bem/Tbx1+
FVB.Cg-Tbx1tm1Bem
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 3 of 29 had outflow tract and pharyngeal arch artery abnormalities including 1 with teratology of fallot with pulmonary atresia, 1 with double outlet right ventricle, and 1 with a retroesophageal right subclavian artery

hearing/vestibular/ear
• 10 of 20 had middle ear abnormalities apparent upon dissection including chronic otitis media, infiltration of inflammatory cells, thickening of the middle ear submucosa, thickening of the bony wall of the bulla, middle ear fluid accumulation, hyperplasia of ciliated cells and associated hearing loss
• the average ABR threshold was 46 dB compared to 29 dB in wild-type mice

immune system


Mouse Genome Informatics
ht7
    Tbx1tm1Bem/Tbx1+
involves: 129 * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• about 25% of embryos show cardiovascular defects at E17.5


Mouse Genome Informatics
ht8
    Tbx1tm1Bem/Tbx1+
involves: 129/Sv * C57BL/6J * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E9.0 - E11, transient ectopic neurogenesis is seen posteroventromedially and later anterodorsolaterally in the otic vesicle

cellular
• at E9.0 - E11, transient ectopic neurogenesis is seen posteroventromedially and later anterodorsolaterally in the otic vesicle


Mouse Genome Informatics
ht9
    Tbx1tm1Bem/Tbx1+
involves: 129/Sv * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 2 of 14 have an abnormal origin of the right subclavian artery, an additional 3 of 14 have a retroesophageal right subclavian artery (1 of these also has an interupted aortic arch), and 1 of 14 have a right subclavian artery that arises from the pulmonary artery
• 3 of 14 have a retroesophageal right subclavian artery
• 1 of 14 heterozyotes has an abnormally high aortic arch
• 1 of 14 has an interrupted aortic arch

craniofacial
• hypotrophic fourth arch at E10.5

embryogenesis
• hypotrophic fourth arch at E10.5

Mouse Models of Human Disease
OMIM IDRef(s)
DiGeorge Syndrome; DGS 188400 J:67796
Velocardiofacial Syndrome 192430 J:67796


Mouse Genome Informatics
cx10
    Eya1tm1Rilm/Eya1+
Tbx1tm1Bem/Tbx1+

involves: 129 * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• about 73% of embryos show cardiovascular defects at E17.5


Mouse Genome Informatics
cx11
    Six1tm1Mair/Six1tm1Mair
Tbx1tm1Bem/Tbx1tm1Bem

involves: 129 * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• about 63% of embryos show cardiovascular defects at E17.5


Mouse Genome Informatics
cx12
    Eya1tm1Rilm/Eya1tm1Rilm
Tbx1tm1Bem/Tbx1tm1Bem

involves: 129 * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• 100% of embryos display a single outflow vessel


Mouse Genome Informatics
cx13
    Ripply3tm1Sjt/Ripply3tm1Sjt
Tbx1tm1Bem/Tbx1tm1Bem

involves: 129/Sv * 129S1/Sv * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• absent in the caudal branchial region

cardiovascular system
• at E18.5 the phenotype is identical to mice homozygous null for Tbx1 alone


Mouse Genome Informatics
cx14
    Ripply3tm1Sjt/Ripply3+
Tbx1tm1Bem/Tbx1+

involves: 129/Sv * 129S1/Sv * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• hypotrophic fourth arch at E10.5

craniofacial
• hypotrophic fourth arch at E10.5


Mouse Genome Informatics
cx15
    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