Phenotypes associated with this allele

• Allele Symbol: Tbx1^tm1Pa
• Allele Name: targeted mutation 1, Virginia Papaioannou
• Allele ID: MGI:2179190
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tbx1^tm1Pa/Tbx1^tm1Pa	either: (involves: 129) or (involves: 129 * C57BL/6) or (involves: 129 * C57BL/6 * Swiss Webster)	MGI:3586912
hm2	Tbx1^tm1Pa/Tbx1^tm1Pa	involves: 129 * C57BL/6	MGI:3586919
hm3	Tbx1^tm1Pa/Tbx1^tm1Pa	involves: 129S1/Sv * 129X1/SvJ	MGI:3850161
ht4	Tbx1^tm1Pa/Tbx1^+	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ	MGI:3586914
ht5	Tbx1^tm1Pa/Tbx1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * Swiss Webster	MGI:3586915
cx6	Myf5^tm2Tajb/Myf5^+ Tbx1^tm1Pa/Tbx1^tm1Pa	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3850163
cx7	Myf5^tm2Tajb/Myf5^tm2Tajb Tbx1^tm1Pa/Tbx1^tm1Pa	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3850162
cx8	Bmp2^tm1Brd/Bmp2^+ Tbx1^tm1Pa/Tbx1^+	involves: 129/Sv * C57BL/6	MGI:3611300

Genotype
MGI:3586912

hm1

• Allelic Composition: Tbx1^tm1Pa/Tbx1^tm1Pa
• Genetic Background: either: (involves: 129) or (involves: 129 * C57BL/6) or (involves: 129 * C57BL/6 * Swiss Webster)

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

mortality/aging

neonatal lethality, complete penetrance ( J:70730 )

• homozygous embryos are present in normal numbers 1 day before birth but following Caesarian section fail to inflate their lungs

embryo

abnormal pharyngeal arch morphology ( J:70730 )

• at E8.5, E9.5, E10.5 and E12.5 only the first pharyngeal arch is present unlike in wild-type mice where four pharyngeal arches are present by E10.5

• abnormalities are found in derivatives of all of the pharyngeal arch structures

abnormal pharyngeal arch artery morphology ( J:70730 )

• at E11.5 only a single large aortic arch is present on each side; however, small pulmonary arteries are present

abnormal fourth pharyngeal arch morphology ( J:70730 )

absent second pharyngeal arch ( J:70730 )

abnormal third pharyngeal arch morphology ( J:70730 )

decreased embryo size ( J:70730 )

abnormal pharyngeal pouch morphology ( J:70730 )

• at E8.5, E9.5, E10.5 and E12.5 only the first pharyngeal pouch is present unlike in wild-type mice where where four pharyngeal pouches are present by E10.5

craniofacial

abnormal cranium morphology ( J:70730 )

fusion of basioccipital and basisphenoid bone ( J:70730 )

• the basioccipital and basispenoid bones are fused

abnormal temporal bone morphology ( J:70730 )

abnormal zygomatic arch morphology ( J:70730 )

• the zygomatic arch is abnormal

absent mandibular coronoid process ( J:70730 )

• the mandible lacks the coronoid process

short mandible ( J:70730 )

• the mandible is disproportionately short

micrognathia ( J:70730 )

abnormal middle ear ossicle morphology ( J:70730 )

abnormal pharyngeal arch morphology ( J:70730 )

• at E8.5, E9.5, E10.5 and E12.5 only the first pharyngeal arch is present unlike in wild-type mice where four pharyngeal arches are present by E10.5

• abnormalities are found in derivatives of all of the pharyngeal arch structures

abnormal pharyngeal arch artery morphology ( J:70730 )

• at E11.5 only a single large aortic arch is present on each side; however, small pulmonary arteries are present

abnormal fourth pharyngeal arch morphology ( J:70730 )

absent second pharyngeal arch ( J:70730 )

abnormal third pharyngeal arch morphology ( J:70730 )

abnormal facial morphology ( J:70730 )

• homozygotes have abnormal facial structures

abnormal upper incisor morphology ( J:70730 )

• the upper incisors are missing or malformed in 3 of 10 homozygotes

absent upper incisors ( J:70730 )

abnormal palatal shelf fusion at midline ( J:70730 )

• the bony elements of the palatine and maxillary shelves never fuse

• at E17.5, there is variable fusion of the epithelium of the palatal shelves from nearly complete fusion to no fusion at all

cleft secondary palate ( J:70730 )

lowered ear position ( J:70730 )

• when present outer ears are low set and abnormally folded

abnormal ear shape ( J:70730 )

• when present outer ears are low set and abnormally folded

absent outer ear ( J:70730 )

hearing/vestibular/ear

abnormal middle ear ossicle morphology ( J:70730 )

lowered ear position ( J:70730 )

• when present outer ears are low set and abnormally folded

abnormal ear shape ( J:70730 )

• when present outer ears are low set and abnormally folded

absent outer ear ( J:70730 )

small otic vesicle ( J:70730 )

• at E9.5, the otic vesicle appears smaller and thickened

abnormal semicircular canal morphology ( J:70730 )

• semicircular canals are poorly developed

abnormal tympanic ring morphology ( J:70730 )

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:70730 )

• at E11.5 only a single large aortic arch is present on each side; however, small pulmonary arteries are present

right aortic arch ( J:70730 )

• 2 of 12 homozygotes had right aortic arches

double aortic arch ( J:70730 )

• 1 of 12 homozygotes had a double aortic arch

persistent truncus arteriosus ( J:70730 )

• at E12.5 the aorticopulmonary septum is absent

immune system

abnormal thymus development ( J:70730 )

• at E10.5 and E12.5, the thymus and parathyroid primordia are absent

athymia ( J:70730 )

endocrine/exocrine glands

absent parathyroid glands ( J:70730 )

• the parathyroid gland is absent but the thyroid gland is present

abnormal thymus development ( J:70730 )

• at E10.5 and E12.5, the thymus and parathyroid primordia are absent

athymia ( J:70730 )

homeostasis/metabolism

hydrops fetalis ( J:70730 )

• late term and neonatal homozygotes appear edematous

respiratory system

small cricoid cartilage ( J:70730 )

• at E14.5 and E17.5, the cricoid cartilage is small and fragmentary

small thyroid cartilage ( J:70730 )

• at E14.5 and E17.5, the thyroid cartilage is small and fragmentary

pharynx stenosis ( J:70730 )

• at E10.5 and E12.5 the pharynx is narrow and constricted laterally

respiratory failure ( J:70730 )

• after a Caesarian homozygotes display a gasping reflex but fail to inflate their lungs

skeleton

abnormal cranium morphology ( J:70730 )

fusion of basioccipital and basisphenoid bone ( J:70730 )

• the basioccipital and basispenoid bones are fused

abnormal temporal bone morphology ( J:70730 )

abnormal zygomatic arch morphology ( J:70730 )

• the zygomatic arch is abnormal

abnormal upper incisor morphology ( J:70730 )

• the upper incisors are missing or malformed in 3 of 10 homozygotes

absent upper incisors ( J:70730 )

absent mandibular coronoid process ( J:70730 )

• the mandible lacks the coronoid process

short mandible ( J:70730 )

• the mandible is disproportionately short

micrognathia ( J:70730 )

abnormal middle ear ossicle morphology ( J:70730 )

small cricoid cartilage ( J:70730 )

• at E14.5 and E17.5, the cricoid cartilage is small and fragmentary

small thyroid cartilage ( J:70730 )

• at E14.5 and E17.5, the thyroid cartilage is small and fragmentary

abnormal cervical atlas morphology ( J:70730 )

absent arcus anterior ( J:70730 )

• the atlas lacks the anterior arch

growth/size/body

abnormal facial morphology ( J:70730 )

• homozygotes have abnormal facial structures

abnormal upper incisor morphology ( J:70730 )

• the upper incisors are missing or malformed in 3 of 10 homozygotes

absent upper incisors ( J:70730 )

abnormal palatal shelf fusion at midline ( J:70730 )

• the bony elements of the palatine and maxillary shelves never fuse

• at E17.5, there is variable fusion of the epithelium of the palatal shelves from nearly complete fusion to no fusion at all

cleft secondary palate ( J:70730 )

lowered ear position ( J:70730 )

• when present outer ears are low set and abnormally folded

abnormal ear shape ( J:70730 )

• when present outer ears are low set and abnormally folded

absent outer ear ( J:70730 )

decreased embryo size ( J:70730 )

short neck ( J:70730 )

• homozygotes have a short neck region

hematopoietic system

abnormal thymus development ( J:70730 )

• at E10.5 and E12.5, the thymus and parathyroid primordia are absent

athymia ( J:70730 )

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:70730 )

• the bony elements of the palatine and maxillary shelves never fuse

• at E17.5, there is variable fusion of the epithelium of the palatal shelves from nearly complete fusion to no fusion at all

cleft secondary palate ( J:70730 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:70730
velocardiofacial syndrome		DOID:12583	OMIM:192430	J:70730

Genotype
MGI:3586919

hm2

• Allelic Composition: Tbx1^tm1Pa/Tbx1^tm1Pa
• Genetic Background: involves: 129 * C57BL/6

hearing/vestibular/ear

abnormal external auditory canal morphology ( J:96463 )

• the external acoustic meatus invaginates normally but has a slightly abnormal trajectory

small otic vesicle ( J:96463 )

• at E9.5, the otic vesicles appear morphologically normal, but by E10.5 they are smaller and rounder in the ventral area than normal

absent cochlea ( J:96463 )

• at birth, no cochlear structures are identified

absent inner ear vestibule ( J:96463 )

• at birth, no vestibular structures are identified

dilated endolymphatic duct ( J:96463 )

• at E10.5, the endolymphatic tube primordium, the only recognizable structure, appears larger than normal

• at birth, the endolymphatic duct is readily discernible and histologically unaffected, albeit larger than normal

abnormal otic capsule morphology ( J:96463 )

• at birth, otic capsules are hardly distinguishable from surrounding cartilaginous structures and appear as small vesicles of variable shape

inner ear hypoplasia ( J:96463 )

• newborn homozygotes exhibit severely hypoplastic inner ears that appear as a pair of small hollow cartilaginous vesicles with a few residual sensory patches identified in the inner ear epithelium

• no vestibular or cochlear structures are detectable; however, the endolymphatic duct and the cochleovestibular ganglia are still identifiable

abnormal middle ear morphology ( J:96463 )

abnormal incus morphology ( J:96463 )

• the incus is reduced to a small cartilaginous nodule

abnormal malleus morphology ( J:96463 )

• the malleus is slightly hypoplastic and the neck is thinner, but all of the basic elements are present

thin malleus neck ( J:96463 )

malleus hypoplasia ( J:96463 )

absent stapes ( J:96463 )

decreased tympanic ring size ( J:96463 )

• the tympanic ring is reduced in length an thicker than normal

craniofacial

abnormal hyoid bone morphology ( J:96463 )

abnormal incus morphology ( J:96463 )

• the incus is reduced to a small cartilaginous nodule

abnormal malleus morphology ( J:96463 )

• the malleus is slightly hypoplastic and the neck is thinner, but all of the basic elements are present

thin malleus neck ( J:96463 )

malleus hypoplasia ( J:96463 )

absent stapes ( J:96463 )

abnormal pharyngeal arch morphology ( J:96463 )

• the first arch is present but the rest of the arches are absent or strongly reduced

absent second pharyngeal arch ( J:96463 )

• at E9.5, the second arches are absent or stongly hypoplastic

absent third pharyngeal arch ( J:96463 )

• at E9.5, the third arches are absent or stongly hypoplastic

abnormal external auditory canal morphology ( J:96463 )

• the external acoustic meatus invaginates normally but has a slightly abnormal trajectory

nervous system

abnormal facial nerve morphology ( J:96463 )

• cranial nerve V is fused to cranial nerves VII/VIII

abnormal trigeminal nerve morphology ( J:96463 )

• cranial nerve V is fused to cranial nerves VII/VIII

abnormal vestibulocochlear nerve morphology ( J:96463 )

• cranial nerve V is fused to cranial nerves VII/VIII

respiratory system

abnormal thyroid cartilage morphology ( J:96463 )

skeleton

abnormal hyoid bone morphology ( J:96463 )

abnormal incus morphology ( J:96463 )

• the incus is reduced to a small cartilaginous nodule

abnormal malleus morphology ( J:96463 )

• the malleus is slightly hypoplastic and the neck is thinner, but all of the basic elements are present

thin malleus neck ( J:96463 )

malleus hypoplasia ( J:96463 )

absent stapes ( J:96463 )

abnormal thyroid cartilage morphology ( J:96463 )

embryo

abnormal neural crest cell migration ( J:96463 )

• neural crest cell migration in the second and more caudal branchial arches is severely compromised

• neural crest cells from rhombomere 4 abnormally migrate into the first branchial arch

abnormal pharyngeal arch morphology ( J:96463 )

• the first arch is present but the rest of the arches are absent or strongly reduced

absent second pharyngeal arch ( J:96463 )

• at E9.5, the second arches are absent or stongly hypoplastic

absent third pharyngeal arch ( J:96463 )

• at E9.5, the third arches are absent or stongly hypoplastic

cellular

abnormal neural crest cell migration ( J:96463 )

• neural crest cell migration in the second and more caudal branchial arches is severely compromised

• neural crest cells from rhombomere 4 abnormally migrate into the first branchial arch

growth/size/body

abnormal external auditory canal morphology ( J:96463 )

• the external acoustic meatus invaginates normally but has a slightly abnormal trajectory

Genotype
MGI:3850161

hm3

• Allelic Composition: Tbx1^tm1Pa/Tbx1^tm1Pa
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

growth/size/body

abnormal laryngeal muscle morphology ( J:94411 )

• laryngeal muscles when present are extremely hypoplastic

muscle

abnormal laryngeal muscle morphology ( J:94411 )

• laryngeal muscles when present are extremely hypoplastic

abnormal myogenesis ( J:94411 )

• at E9.5, mandibular mesenchyme is abnormally patterned with expansion of the expression domains of Tbx2, Tbx3, Dlx4, Msx2, and Prx2 in the proximal arch region

• at E10.5, muscle masses derived from the first and second branchial arches and muscles that normally form in the caudal pharyngeal region are absent and the length of the hypoglossal cord is reduced

• at E12.5, expression of myogenic regulatory factors indicates that the majority of branchiomeric muscles do not form; however hypobranchial muscle formation is normal

• at E16.5, mandibular arch-derived muscles are frequently hypoplastic and asymmetric or unilateral, with muscle loss more severe on the left side than on the right side

abnormal hypoglossal cord morphology ( J:94411 )

• at E10.5, the length of the hypoglossal cord is reduced

• however, tongue muscle development is not impaired

abnormal pharyngeal muscle morphology ( J:150130 )

• mice exhibit sporadic asymmetric first-arch-derived muscles unlike in wild-type mice

respiratory system

abnormal laryngeal muscle morphology ( J:94411 )

• laryngeal muscles when present are extremely hypoplastic

abnormal pharyngeal muscle morphology ( J:150130 )

• mice exhibit sporadic asymmetric first-arch-derived muscles unlike in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:94411

Genotype
MGI:3586914

ht4

• Allelic Composition: Tbx1^tm1Pa/Tbx1⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ

cardiovascular system

abnormal fourth pharyngeal arch artery morphology ( J:70730 )

• Background Sensitivity: the incidence of this phenotype is increased on an inbred 129 background compared to mixed 129 and C57BL/6 or 129 and Swiss Webster backgrounds

• at E11.5, the fourth aortic arch arteries are either absent or reduced in thickness in 45% of heterozygotes compared to 7% of wild-type embryos

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:70730 )

• Background Sensitivity: the incidence of this phenotype is increased on an inbred 129 background compared to mixed 129 and C57BL/6 or 129 and Swiss Webster backgrounds

• at E11.5, the fourth aortic arch arteries are either absent or reduced in thickness in 45% of heterozygotes compared to 7% of wild-type embryos

embryo

abnormal fourth pharyngeal arch artery morphology ( J:70730 )

• Background Sensitivity: the incidence of this phenotype is increased on an inbred 129 background compared to mixed 129 and C57BL/6 or 129 and Swiss Webster backgrounds

• at E11.5, the fourth aortic arch arteries are either absent or reduced in thickness in 45% of heterozygotes compared to 7% of wild-type embryos

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:70730

Genotype
MGI:3586915

ht5

• Allelic Composition: Tbx1^tm1Pa/Tbx1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * Swiss Webster

cardiovascular system

abnormal fourth pharyngeal arch artery morphology ( J:70730 )

• at E11.5, the fourth aortic arch arteries are either absent or reduced in thickness in 19% of heterozygotes compared to 2% of wild-type embryos

• Background Sensitivity: the incidence of this phenotype is increased on an inbred 129 background compared to mixed 129 and C57BL/6 or 129 and Swiss Webster backgrounds

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:70730 )

• at E11.5, the fourth aortic arch arteries are either absent or reduced in thickness in 19% of heterozygotes compared to 2% of wild-type embryos

• Background Sensitivity: the incidence of this phenotype is increased on an inbred 129 background compared to mixed 129 and C57BL/6 or 129 and Swiss Webster backgrounds

embryo

abnormal fourth pharyngeal arch artery morphology ( J:70730 )

• at E11.5, the fourth aortic arch arteries are either absent or reduced in thickness in 19% of heterozygotes compared to 2% of wild-type embryos

• Background Sensitivity: the incidence of this phenotype is increased on an inbred 129 background compared to mixed 129 and C57BL/6 or 129 and Swiss Webster backgrounds

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:70730

Genotype
MGI:3850163

cx6

• Allelic Composition: Myf5^tm2Tajb/Myf5⁺; Tbx1^tm1Pa/Tbx1^tm1Pa
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

muscle

abnormal pharyngeal muscle morphology ( J:150130 )

• mice exhibit sporadic asymmetric first-arch-derived muscles unlike in wild-type mice

respiratory system

abnormal pharyngeal muscle morphology ( J:150130 )

• mice exhibit sporadic asymmetric first-arch-derived muscles unlike in wild-type mice

Genotype
MGI:3850162

cx7

• Allelic Composition: Myf5^tm2Tajb/Myf5^tm2Tajb; Tbx1^tm1Pa/Tbx1^tm1Pa
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

muscle

abnormal pharyngeal muscle morphology ( J:150130 )

• first-arch-derived muscles are absent in almost all mice

respiratory system

abnormal pharyngeal muscle morphology ( J:150130 )

• first-arch-derived muscles are absent in almost all mice

Genotype
MGI:3611300

cx8

• Allelic Composition: Bmp2^tm1Brd/Bmp2⁺; Tbx1^tm1Pa/Tbx1⁺
• Genetic Background: involves: 129/Sv * C57BL/6

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:80764 )

• double heterozygous newborns show malformations in the aortic arch-derived arterial tree at a frequency similar to that observed in mice heterozygous for Tbx1^tm1Pa (27% vs 25%, respectively)

• notably, pharyngeal glands appear unaffected in both groups of mice

craniofacial

abnormal pharyngeal arch artery morphology ( J:80764 )

• double heterozygous newborns show malformations in the aortic arch-derived arterial tree at a frequency similar to that observed in mice heterozygous for Tbx1^tm1Pa (27% vs 25%, respectively)

• notably, pharyngeal glands appear unaffected in both groups of mice

embryo

abnormal pharyngeal arch artery morphology ( J:80764 )

• double heterozygous newborns show malformations in the aortic arch-derived arterial tree at a frequency similar to that observed in mice heterozygous for Tbx1^tm1Pa (27% vs 25%, respectively)

• notably, pharyngeal glands appear unaffected in both groups of mice