Phenotypes associated with this allele

• Allele Symbol: Tbx1^tm2.2Bem
• Allele Name: targeted mutation 2.2, Bernice E Morrow
• Allele ID: MGI:3619150
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tbx1^tm2.2Bem/Tbx1^tm2.2Bem	involves: 129/Sv * C57BL/6J * SJL * Swiss Webster	MGI:3619801
cn2	Tbx1^tm2.1Bem/Tbx1^tm2.2Bem Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129 * C57BL/6J * SJL * Swiss Webster	MGI:3619802
cn3	Tbx1^tm2.1Bem/Tbx1^tm2.2Bem Tg(Pax2-cre)1Akg/0	involves: 129 * C57BL/6 * SJL	MGI:3703706

Genotype
MGI:3619801

hm1

• Allelic Composition: Tbx1^tm2.2Bem/Tbx1^tm2.2Bem
• Genetic Background: involves: 129/Sv * C57BL/6J * SJL * Swiss Webster

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, complete penetrance ( J:105980 )

• mice do not survive beyond the neonatal period

craniofacial

absent facial muscle ( J:105980 )

• null mutants lack 2nd pharyngeal arch-derived facial muscles

cardiovascular system

abnormal interventricular septum morphology ( J:105980 )

• in mutants the left ventricle communicates with the right through a large VSD

growth/size/body

absent facial muscle ( J:105980 )

• null mutants lack 2nd pharyngeal arch-derived facial muscles

muscle

absent facial muscle ( J:105980 )

• null mutants lack 2nd pharyngeal arch-derived facial muscles

Genotype
MGI:3619802

cn2

• Allelic Composition: Tbx1^tm2.1Bem/Tbx1^tm2.2Bem; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129 * C57BL/6J * SJL * Swiss Webster

mortality/aging

neonatal lethality, complete penetrance ( J:105980 , J:109536 )

• mice do not survive beyond the neonatal period (J:105980)

• mutants die between E18.5 and E20.5 with multiple defects of the pharyngeal apparatus (J:109536)

homeostasis/metabolism

skin edema ( J:105980 )

• at E17.5, mutants appear edematous

craniofacial

abnormal craniofacial bone morphology ( J:109536 )

• at E17.5, mutants display severe malformations of craniofacial bone structures

fusion of basioccipital and basisphenoid bone ( J:105980 , J:109536 )

• at E17.5, mutants display fused basisphenoid and basioccipital bones (J:109536)

temporal bone hypoplasia ( J:105980 )

absent zygomatic arch ( J:105980 )

• zygomatic arch is missing

hyoid bone hypoplasia ( J:105980 )

• hyoid bone is hypoplastic

short mandible ( J:105980 )

• mandible is shorter than in wild-type

decreased middle ear ossicle number ( J:105980 , J:109536 )

• middle ear is absent (J:105980)

• at E15.5-E17.5, middle ear ossicles do not start the condensation process and thus fail to develop (J:109536)

absent masseter muscle ( J:105980 )

• in conditional mutants, the masseter muscle is absent

absent pterygoid muscle ( J:105980 )

• in conditional mutants, pterygoid muscles are absent

cleft secondary palate ( J:105980 , J:109536 )

• observed at E17.5 (J:105980)

• at E17.5, mutants exhibit cleft palate (J:109536)

absent outer ear ( J:105980 , J:109536 )

• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop (J:109536)

hearing/vestibular/ear

decreased middle ear ossicle number ( J:105980 , J:109536 )

• middle ear is absent (J:105980)

• at E15.5-E17.5, middle ear ossicles do not start the condensation process and thus fail to develop (J:109536)

absent outer ear ( J:105980 , J:109536 )

• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop (J:109536)

abnormal middle ear development ( J:109536 )

• at E10.5, the pharyngeal endoderm fails to invaginate toward the surface endoderm to form the tubotympanic recess, resulting in disruption of middle ear development

small otic vesicle ( J:109536 )

• at E10.5 or later

otic vesicle hypoplasia ( J:109536 )

• early otic vesicle development is normal; however, the structure is slightly hypoplastic by E10.5 and appears cystic at E17.5

• in contrast, periotic mesenchyme development appears normal

absent cochlea ( J:109536 )

absent semicircular canals ( J:109536 )

absent inner ear vestibule ( J:109536 )

abnormal endolymphatic duct morphology ( J:109536 )

• at E17.5, mutants display a cystic endolymphatic duct

otic capsule hypoplasia ( J:109536 )

• at E17.5, the otic capsule is hypoplastic

absent inner ear ( J:109536 )

• at E17.5, mutants show complete aplasia of inner ear sensory organs

inner ear hypoplasia ( J:109536 )

• at E17.5, mutants exhibit severe hypoplasia of the inner ear, developing only a cystic OV and endolymphatic duct

absent tubotympanic recess ( J:109536 )

• at E10.5, the pharyngeal endoderm fails to invaginate toward the surface endoderm to form the tubotympanic recess

absent tympanic ring ( J:105980 , J:109536 )

• at E17.5, mutants lack tympanic rings (J:109536)

respiratory system

pharynx hypoplasia ( J:105980 )

• pharynx in conditional null embryos is hypoplastic, lacking distal arches; the first pouch appears to be hypoplastic

skeleton

abnormal craniofacial bone morphology ( J:109536 )

• at E17.5, mutants display severe malformations of craniofacial bone structures

fusion of basioccipital and basisphenoid bone ( J:105980 , J:109536 )

• at E17.5, mutants display fused basisphenoid and basioccipital bones (J:109536)

temporal bone hypoplasia ( J:105980 )

absent zygomatic arch ( J:105980 )

• zygomatic arch is missing

hyoid bone hypoplasia ( J:105980 )

• hyoid bone is hypoplastic

short mandible ( J:105980 )

• mandible is shorter than in wild-type

decreased middle ear ossicle number ( J:105980 , J:109536 )

• middle ear is absent (J:105980)

• at E15.5-E17.5, middle ear ossicles do not start the condensation process and thus fail to develop (J:109536)

cardiovascular system

abnormal aortic arch morphology ( J:105980 )

• all null mutants have aortic arch defects

retroesophageal right subclavian artery ( J:105980 )

• mutants have retroesophageal right subclavian artery

abnormal cardiac outflow tract development ( J:105980 )

• at E10.5 all conditional mutants display hypoplasia of the outflow tract

persistent truncus arteriosus ( J:105980 )

• all conditional null mutants have a single outflow tract

ventricular septal defect ( J:105980 )

• in mutants the left ventricle communicates with the right through a large VSD

endocrine/exocrine glands

absent parathyroid glands ( J:105980 )

athymia ( J:105980 )

small thyroid gland ( J:105980 )

• thyroid glands are smaller than wild-type and ectopically placed in conditional null embryos while conditional heterozygous embryos have ectopically placed thyroid glands

immune system

athymia ( J:105980 )

muscle

absent masseter muscle ( J:105980 )

• in conditional mutants, the masseter muscle is absent

absent pterygoid muscle ( J:105980 )

• in conditional mutants, pterygoid muscles are absent

hematopoietic system

athymia ( J:105980 )

digestive/alimentary system

cleft secondary palate ( J:105980 , J:109536 )

• observed at E17.5 (J:105980)

• at E17.5, mutants exhibit cleft palate (J:109536)

nervous system

abnormal vestibulocochlear ganglion morphology ( J:109536 )

• at E10.5, the otic vesicle is surrounded by an expanded cochleovestibular ganglion rudiment

• at E11.5, the cochleovestibular ganglion is duplicated around the otic vesicle anterior-posterior midline

embryo

abnormal pharyngeal pouch morphology ( J:109536 )

• at E10.5, the first pharyngeal pouch fails to outgrow, preventing middle ear bone condensations

integument

skin edema ( J:105980 )

• at E17.5, mutants appear edematous

growth/size/body

absent zygomatic arch ( J:105980 )

• zygomatic arch is missing

hyoid bone hypoplasia ( J:105980 )

• hyoid bone is hypoplastic

short mandible ( J:105980 )

• mandible is shorter than in wild-type

absent masseter muscle ( J:105980 )

• in conditional mutants, the masseter muscle is absent

absent pterygoid muscle ( J:105980 )

• in conditional mutants, pterygoid muscles are absent

cleft secondary palate ( J:105980 , J:109536 )

• observed at E17.5 (J:105980)

• at E17.5, mutants exhibit cleft palate (J:109536)

absent outer ear ( J:105980 , J:109536 )

• at E15.5-E17.5, the pinnae do not start the condensation process and thus fail to develop (J:109536)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:105980 , J:109536

Genotype
MGI:3703706

cn3

• Allelic Composition: Tbx1^tm2.1Bem/Tbx1^tm2.2Bem; Tg(Pax2-cre)1Akg/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

hearing/vestibular/ear

small otic vesicle ( J:109536 )

• at E10.5

otic vesicle hypoplasia ( J:109536 )

• early otic vesicle development is normal; however, the structure is hypoplastic at E10.5

• in contrast, periotic mesenchyme development appears normal

abnormal inner ear morphology ( J:109536 )

• at E17.5, 12 of 16 mutant ears show complete failure of inner ear development while the remaining appear completely normal

• in contrast, formation of the otic capsule and development of middle ear ossicles and pinnae is clearly normal at E17.5 and in adulthood

absent cochlea ( J:109536 )

• in 12 of 16 mutant inner ears

absent semicircular canals ( J:109536 )

• in 12 of 16 mutant inner ears

absent inner ear vestibule ( J:109536 )

• in 12 of 16 mutant inner ears

absent inner ear ( J:109536 )

• at E17.5, 6 of 8 mutants show complete aplasia of inner ear sensory organs

inner ear hypoplasia ( J:109536 )

• at E17.5, 6 of 8 mutant embryos display a severely hypoplastic inner ear

• severe hypoplasia is bilateral and present in 12/16 mutant ears

• at E17.5, the inner ear persists in a rudimentary otic vesicle stage

increased or absent threshold for auditory brainstem response ( J:109536 )

• 3 of 5 adults exhibit no hearing on either the left or right side, as determined by auditory brainstem response testing

• the remaining two adults display normal hearing, consistent with the incomplete penetrance of the inner ear phenotype noted at E17.5

sensorineural hearing loss ( J:109536 )

• in 3 of 5 adult mutants

nervous system

abnormal vestibulocochlear ganglion morphology ( J:109536 )

• at E10.5, a smaller otic vesicle is surrounded by an expanded cochleovestibular ganglion

• at E11.5, the cochleovestibular ganglion is duplicated around the otic vesicle anterior-posterior midline

embryo

embryo phenotype ( J:109536 )

N • at E10.5, mutants show normal invagination of the pharyngeal endoderm to form the future tubotympanic recess

craniofacial

craniofacial phenotype ( J:109536 )

N • mutants survive in normal Mendelian ratios through adulthood and show normal craniofacial bone development at E17.5