Phenotypes associated with this allele

• Allele Symbol: Tbx1^tm1Bld
• Allele Name: targeted mutation 1, Antonio Baldini
• Allele ID: MGI:2179136
• Summary: 36 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tbx1^tm1Bld/Tbx1^tm1Bld	involves: 129S7/SvEvBrd	MGI:3640317
hm2	Tbx1^tm1Bld/Tbx1^tm1Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:3610987
ht3	Tbx1^tm1Bld/Tbx1^+	B6.129S7-Tbx1^tm1Bld	MGI:4410365
ht4	Tbx1^tm1Bld/Tbx1^+	B6.Cg-Tyr^c-Brd Tbx1^tm1Bld	MGI:3640308
ht5	Tbx1^tm1Bld/Tbx1^+	involves: 129S7/SvEvBrd	MGI:3713494
ht6	Tbx1^tm1Bld/Tbx1^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3610986
ht7	Tbx1^tm1Bld/Tbx1^+	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:7543764
ht8	Tbx1^tm1Bld/Tbx1^+	involves: 129S7/SvEvBrd * C57BL/6J	MGI:5583879
ht9	Tbx1^m1Jlk/Tbx1^tm1Bld	involves: 129	MGI:3841292
ht10	Tbx1^tm1Bld/Tbx1^tm6(cre)Bld	involves: 129S7/SvEvBrd	MGI:5551756
ht11	Tbx1^tm1Bld/Tbx1^tm7.1Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:5140364
ht12	Tbx1^tm1Bld/Tbx1^tm2Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:3046798
ht13	Tbx1^tm1Bld/Tbx1^tm1(Fgf8)Vite	involves: 129S7/SvEvBrd * C57BL/6	MGI:3641317
ht14	Tbx1^tm1Bld/Tbx1^tm5Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:3686780
ht15	Tbx1^tm1Bld/Tbx1^tm8.1Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:5140381
cn16	Tbx1^tm1Bld/Tbx1^tm2.1Bem Tfap2a^tm1(cre)Moon/Tfap2a^+	either: (involves: 129/Sv * C57BL/6 * SJL) or (involves: 129/Sv * C57BL/6J * CBA * SJL)	MGI:4410378
cn17	Tbx1^tm1Bld/Tbx1^tm3Bld Tg(Tek-cre)1Ywa/0	involves: 129S7/SvEvBrd * C57BL/6	MGI:3046801
cn18	Nkx2-5^tm1(cre)Rjs/Nkx2-5^+ Tbx1^tm1Bld/Tbx1^tm3Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:3046805
cn19	Tbx1^tm1Bld/Tbx1^tm3Bld Tg(Myh6-cre)2182Mds/0	involves: 129S7/SvEvBrd * C57BL/6	MGI:3046803
cn20	Hoxa3^tm1(cre)Moon/Hoxa3^+ Tbx1^tm3Bld/Tbx1^tm1Bld	involves: 129S7/SvEvBrd * C57BL/6	MGI:3641322
cn21	Tbx1^tm1Bld/Tbx1^tm3Bld Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:4453459
cn22	Mesp1^tm2(cre)Ysa/Mesp1^+ Tbx1^tm1Bld/Tbx1^tm5Bld	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3686782
cn23	Mesp1^tm2(cre)Ysa/Mesp1^+ Tbx1^tm1Bld/Tbx1^tm3Bld	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3686776
cn24	Setd5^tm1c(EUCOMM)Wtsi/Setd5^+ Tbx1^tm1Bld/Tbx1^+ Tmem163^Tg(ACTB-cre)2Mrt/Tmem163^+	involves: 129S7/SvEvBrd * C57BL/6 * FVB/N	MGI:7543763
cn25	Gt(ROSA)26Sor^tm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor^tm1(Tbx1/GFP)Bem Tbx1^tm1Bld/Tbx1^tm6(cre)Bld	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:5551755
cn26	Gt(ROSA)26Sor^tm1(Tbx1/GFP)Bem/Gt(ROSA)26Sor^+ Tbx1^tm1Bld/Tbx1^tm6(cre)Bld	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:5551754
cn27	Tbx1^tm1Bld/Tbx1^tm3Bld Tg(Tek-cre)1Ywa/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:4453460
cx28	Chd7^Whi/Chd7^+ Tbx1^tm1Bld/Tbx1^+	B6.Cg-Chd7^Whi Tbx1^tm1Bld	MGI:4410367
cx29	Chd7^Gt(XK403)Byg/Chd7^+ Tbx1^tm1Bld/Tbx1^+	either: (involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6) or (involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * CD-1)	MGI:4410364
cx30	Kat6a^tm1Avo/Kat6a^+ Tbx1^tm1Bld/Tbx1^+	involves: 129 * 129S7/SvEvBrd * BALB/c * C57BL/6	MGI:5447056
cx31	Fgf8^tm1.4Mrt/Fgf8^+ Tbx1^tm1Bld/Tbx1^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * ICR	MGI:3611260
cx32	Smad7^Gt(YHC053)Byg/Smad7^+ Tbx1^tm1Bld/Tbx1^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J	MGI:5583877
cx33	Fgf15^tm1Sms/Fgf15^+ Tbx1^tm1Bld/Tbx1^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6	MGI:3639490
cx34	Tbx1^tm1Bld/Del(16Es2el-Ufd1l)217Bld	involves: 129S5/SvEvBrd * 129S7/SvEvBrd * C57BL/6	MGI:3640192
cx35	Tbx1^tm1Bld/Del(16Es2el-Ufd1l)217Bld	involves: 129S7/SvEvBrd	MGI:3713495
cx36	Kat6a^tm2.2Avo/Kat6a^+ Tbx1^tm1Bld/Tbx1^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:5447057

Genotype
MGI:3640317

hm1

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm1Bld
• Genetic Background: involves: 129S7/SvEvBrd

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

Cleft palate, absent thymus and ear and cardiovascular abnormalities in Tbx1^tm1Bld/Tbx1^tm1Bld mice

craniofacial

absent sixth pharyngeal arch artery ( J:67409 )

• absent

absent third pharyngeal arch artery ( J:67409 )

• absent

abnormal palatal shelf fusion at midline ( J:110378 )

• Background Sensitivity: only 57% of mice on a 129S7/SvEvBrd background display complete lack of fusion of palatal shelves, while in 21% the palate is closed, and is almost completely closed in another 21%

abnormal fourth pharyngeal arch morphology ( J:110378 )

• hypoplastic at E10.5

absent fourth pharyngeal arch artery ( J:67409 )

• absent

small second pharyngeal arch ( J:67409 )

cleft palate ( J:146769 )

abnormal outer ear morphology ( J:146769 )

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:110378 )

• Background Sensitivity: only 57% of mice on a 129S7/SvEvBrd background display complete lack of fusion of palatal shelves, while in 21% the palate is closed, and is almost completely closed in another 21%

cleft palate ( J:146769 )

cardiovascular system

absent fourth pharyngeal arch artery ( J:67409 )

• absent

absent sixth pharyngeal arch artery ( J:67409 )

• absent

absent third pharyngeal arch artery ( J:67409 )

• absent

persistent truncus arteriosus ( J:146769 )

embryo

absent sixth pharyngeal arch artery ( J:67409 )

• absent

absent third pharyngeal arch artery ( J:67409 )

• absent

abnormal fourth pharyngeal arch morphology ( J:110378 )

• hypoplastic at E10.5

absent fourth pharyngeal arch artery ( J:67409 )

• absent

small second pharyngeal arch ( J:67409 )

cellular

increased apoptosis ( J:159824 )

• at E16.5 but not E14.5, mice exhibit an increase in apoptosis adjacent to the mesenteric artery unlike in wild-type mice

homeostasis/metabolism

skin edema ( J:159824 )

• at E14.5

immune system

athymia ( J:146769 )

abnormal lymphatic vessel morphology ( J:159824 )

• at E18.5, mice exhibit fewer mesenteric lymph vessels in the gastrointestinal tract, diaphragm, skin, and heart compared with wild-type mice

abnormal lymphangiogenesis ( J:159824 )

• development of gastrointestinal lymphatic vasculature fails unlike in wild-type mice

lymphangiectasis ( J:159824 )

integument

skin edema ( J:159824 )

• at E14.5

hearing/vestibular/ear

abnormal ear morphology ( J:204435 )

• lack of all discernible vestibular and auditory structures except for enlarged endolymphatic ducts

abnormal outer ear morphology ( J:146769 )

abnormal inner ear morphology ( J:146769 )

abnormal endolymphatic duct morphology ( J:204435 )

• enlarged at E14.5

hematopoietic system

athymia ( J:146769 )

endocrine/exocrine glands

athymia ( J:146769 )

growth/size/body

abnormal palatal shelf fusion at midline ( J:110378 )

• Background Sensitivity: only 57% of mice on a 129S7/SvEvBrd background display complete lack of fusion of palatal shelves, while in 21% the palate is closed, and is almost completely closed in another 21%

cleft palate ( J:146769 )

abnormal outer ear morphology ( J:146769 )

Genotype
MGI:3610987

hm2

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm1Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal dorsal aorta morphology ( J:67409 )

• at E10.5, doral aortae connect directly with aortic sac

abnormal pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all homozygotes lack the third, fourth and sixth pharyngeal arch arteries (PAAs); instead, the dorsal aortae connected directly with the aortic sac

abnormal fourth pharyngeal arch artery morphology ( J:110378 )

• hypoplastic at E10.5

absent fourth pharyngeal arch artery ( J:67409 )

• absent at E10.5

absent sixth pharyngeal arch artery ( J:67409 )

• absent at E10.5

absent third pharyngeal arch artery ( J:67409 )

• absent at E10.5

retroesophageal right subclavian artery ( J:76173 )

• at E18.5, homozygotes display an abnormal (retroesophageal) right subclavian artery

abnormal truncus arteriosus septation ( J:76173 )

• homozygotes exhibit aortico-pulmonary septum agenesis due to severe defects in the pharyngeal region and the aortic sac

persistent truncus arteriosus ( J:76173 )

• at term, all homozygotes display truncus arteriosus communis; however, the semilunar valve leaflets appear unaffected

abnormal fetal atrioventricular canal morphology ( J:76173 )

• homozygotes exhibit incorrect alignment between the atrioventricular canal and the outflow tract, as shown by the loss of continuity between truncal leaflets and the mitral valve

abnormal conotruncus morphology ( J:76173 )

• at E9.5, the mutant conotruncal conduit is significantly reduced in diameter

abnormal conotruncus septation ( J:76173 )

• the conal septum is also severely affected: at term, the single arterial orifice is connected exclusively to the right ventricle

perimembraneous ventricular septal defect ( J:76173 )

• at E18.5, homozygotes show large ventricular septal defects that include the perimembranous and infundibular regions

nervous system

abnormal vestibulocochlear ganglion morphology ( J:85072 )

• at E9.5, the mutant cochleo-vestibular ganglion is abnormally (ventrally) positioned, losing its proximity to the VII cranial nerve ganglion

abnormal glossopharyngeal ganglion morphology ( J:76173 )

• the distal ganglia of the mutant glossopharyngeal (IX) and vagus (X) nerves, which derive from the ectodermal placodes, are abnormally fused

abnormal vagus ganglion morphology ( J:76173 )

• the distal ganglia of the mutant glossopharyngeal (IX) and vagus (X) nerves, which derive from the ectodermal placodes, are abnormally fused

abnormal cranial nerve morphology ( J:76173 )

• mutant cranial nerves are formed but their migration paths are abnormal

abnormal accessory nerve morphology ( J:76173 )

• terminal projections of mutant accessory (XI) nerves are misdirected rostrally

abnormal glossopharyngeal nerve morphology ( J:76173 )

• axonal projections appear defasciculated and disordered

glossopharyngeal nerve hypoplasia ( J:76173 )

• the fibers of the glossopharyngeal (IX) nerve are either hypoplastic or bundled to the fibers of the vagus (X) nerve

abnormal trigeminal nerve morphology ( J:76173 )

abnormal mandibular nerve branching ( J:76173 )

• the mandibular branch of the trigeminal (V) nerve is abnormally directed caudally and fuses with the facial (VII) nerve fibers

abnormal vagus nerve morphology ( J:76173 )

• terminal projections of mutant vagus nerves are misdirected rostrally

fusion of glossopharyngeal and vagus nerve ( J:76173 )

• the fibers of the glossopharyngeal (IX) nerve are either hypoplastic or bundled to the fibers of the vagus (X) nerve

hearing/vestibular/ear

abnormal outer ear morphology ( J:85072 )

small otic vesicle ( J:85072 )

• at E9.5, homozygotes exhibit a significantly reduced otocyst with a thickened epithelial wall

• during E9.5-E13.5, the mutant otocyst expands only minimally, indicating failure of subsequent growth and morphogenesis

absent cochlea ( J:85072 )

• at E13.5, the mutant otocyst retains the morphology of an earlier, underdeveloped otocyst; no developing cochlea is observed

absent semicircular canals ( J:85072 )

• at E12.5, the mutant otocyst retains the morphology of an earlier, underdeveloped otocyst; no developing semicircular canals are observed

absent inner ear vestibule ( J:85072 )

• at term, homozygotes exhibit complete absence of a vestibular apparatus

absent inner ear ( J:85072 )

• homozygotes exhibit arrest of inner ear development at an early otocyst stage and after neurogenesis

• notably, the mutant endolymphatic duct grows apparently normally

abnormal middle ear morphology ( J:85072 )

respiratory system

pharynx hypoplasia ( J:76173 )

• at E9.5, homozygotes display a severely hypoplastic pharynx which lacks the characteristic segmented pattern observed in wild-type embryos

craniofacial

abnormal palate development ( J:317609 )

• in early palate development (E11.2-E12.5) shelves are thicker compared to controls but this reverses in later stages (E13.5 - E15.5)

• increase in cell density before elevation is retarded and decreasing density after elevation is absent

abnormal palatal mesenchymal cell proliferation ( J:317609 )

• reduced palatal shelf mesenchymal cell proliferation at E15.5

abnormal secondary palate development ( J:317609 )

• increased palatal protrusion at E14.5 but this reverses at E15.5

• abnormal cell polarity in the antero-posterior subregions

abnormal palatal shelf size ( J:317609 )

decreased palatal shelf size ( J:317609 )

• palatal shelves are smaller than controls at E15.5

increased palatal shelf size ( J:317609 )

• palatal shelves are larger than controls at E14.5

abnormal pharyngeal arch morphology ( J:67409 )

• at E10.5, all homozygotes show a severe developmental impairment of pharyngeal arches

abnormal pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all homozygotes lack the third, fourth and sixth pharyngeal arch arteries (PAAs); instead, the dorsal aortae connected directly with the aortic sac

abnormal fourth pharyngeal arch artery morphology ( J:110378 )

• hypoplastic at E10.5

absent fourth pharyngeal arch artery ( J:67409 )

• absent at E10.5

absent sixth pharyngeal arch artery ( J:67409 )

• absent at E10.5

absent third pharyngeal arch artery ( J:67409 )

• absent at E10.5

small second pharyngeal arch ( J:67409 )

• at E10.5, all homozygotes exhibit hypoplastic second pharyngeal arches relative to wild-type embryos

absent pharyngeal arches ( J:76173 )

• at E9.5, homozygotes lack clearly identifiable branchial arches 3-6

cleft secondary palate ( J:91013 , J:110378 )

• at E18.5, all homozygotes exhibit a cleft palate (J:91013)

• Background Sensitivity: on this mixed background, all mutants have complete cleft secondary palate (J:110378)

abnormal outer ear morphology ( J:85072 )

embryo

abnormal neural crest cell migration ( J:76173 )

• homozygotes show impaired distribution of NC-derived cells, as detected by migratory, postmigratory, and differentiation markers

abnormal pharyngeal arch morphology ( J:67409 )

• at E10.5, all homozygotes show a severe developmental impairment of pharyngeal arches

abnormal pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all homozygotes lack the third, fourth and sixth pharyngeal arch arteries (PAAs); instead, the dorsal aortae connected directly with the aortic sac

abnormal fourth pharyngeal arch artery morphology ( J:110378 )

• hypoplastic at E10.5

absent fourth pharyngeal arch artery ( J:67409 )

• absent at E10.5

absent sixth pharyngeal arch artery ( J:67409 )

• absent at E10.5

absent third pharyngeal arch artery ( J:67409 )

• absent at E10.5

small second pharyngeal arch ( J:67409 )

• at E10.5, all homozygotes exhibit hypoplastic second pharyngeal arches relative to wild-type embryos

absent pharyngeal arches ( J:76173 )

• at E9.5, homozygotes lack clearly identifiable branchial arches 3-6

abnormal pharyngeal pouch morphology ( J:76173 )

• at E9.5, homozygotes lack clearly identifiable branchial pouches 2-4

digestive/alimentary system

abnormal palate development ( J:317609 )

• in early palate development (E11.2-E12.5) shelves are thicker compared to controls but this reverses in later stages (E13.5 - E15.5)

• increase in cell density before elevation is retarded and decreasing density after elevation is absent

abnormal palatal mesenchymal cell proliferation ( J:317609 )

• reduced palatal shelf mesenchymal cell proliferation at E15.5

abnormal secondary palate development ( J:317609 )

• increased palatal protrusion at E14.5 but this reverses at E15.5

• abnormal cell polarity in the antero-posterior subregions

abnormal palatal shelf size ( J:317609 )

decreased palatal shelf size ( J:317609 )

• palatal shelves are smaller than controls at E15.5

increased palatal shelf size ( J:317609 )

• palatal shelves are larger than controls at E14.5

cleft secondary palate ( J:91013 , J:110378 )

• at E18.5, all homozygotes exhibit a cleft palate (J:91013)

• Background Sensitivity: on this mixed background, all mutants have complete cleft secondary palate (J:110378)

cellular

abnormal neural crest cell migration ( J:76173 )

• homozygotes show impaired distribution of NC-derived cells, as detected by migratory, postmigratory, and differentiation markers

growth/size/body

abnormal palate development ( J:317609 )

• in early palate development (E11.2-E12.5) shelves are thicker compared to controls but this reverses in later stages (E13.5 - E15.5)

• increase in cell density before elevation is retarded and decreasing density after elevation is absent

abnormal palatal mesenchymal cell proliferation ( J:317609 )

• reduced palatal shelf mesenchymal cell proliferation at E15.5

abnormal secondary palate development ( J:317609 )

• increased palatal protrusion at E14.5 but this reverses at E15.5

• abnormal cell polarity in the antero-posterior subregions

abnormal palatal shelf size ( J:317609 )

decreased palatal shelf size ( J:317609 )

• palatal shelves are smaller than controls at E15.5

increased palatal shelf size ( J:317609 )

• palatal shelves are larger than controls at E14.5

cleft secondary palate ( J:91013 , J:110378 )

• at E18.5, all homozygotes exhibit a cleft palate (J:91013)

• Background Sensitivity: on this mixed background, all mutants have complete cleft secondary palate (J:110378)

abnormal outer ear morphology ( J:85072 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:67409

Genotype
MGI:4410365

ht3

• Allelic Composition: Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: B6.129S7-Tbx1^tm1Bld

Malformations of the semicircular canals in Chd7^Whi/Chd7⁺, Tbx1^tm1Bld/Tbx1⁺, and Chd7^Whi/Chd7⁺ Tbx1^tm1Bld/Tbx1⁺ mice

hearing/vestibular/ear

abnormal lateral semicircular canal morphology ( J:154590 )

• 56% of mice exhibit lateral canal defects unlike wild-type mice including 33% of mice with thin lateral canal and 22% of mice with ampulla only

absent lateral semicircular canal ( J:154590 )

• in 22% of mice

Genotype
MGI:3640308

ht4

• Allelic Composition: Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: B6.Cg-Tyr^c-Brd Tbx1^tm1Bld

nervous system

decreased prepulse inhibition ( J:110101 )

• PPI is significantly impaired; mice have reduced PPI

Genotype
MGI:3713494

ht5

• Allelic Composition: Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129S7/SvEvBrd

cardiovascular system

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all embryos have an abnormal and hypoplastic fourth branchial arch

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all embryos have an abnormal and hypoplastic fourth branchial arch

embryo

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all embryos have an abnormal and hypoplastic fourth branchial arch

Genotype
MGI:3610986

ht6

• Allelic Composition: Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

mortality/aging

postnatal lethality ( J:110620 )

• at weaning there is 4.1% loss of homozygotes compared to expected numbers

cardiovascular system

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all heterozygotes exhibit at least one abnormal fourth pharyngeal arch artery (PAA), that is typically scored as abnormally small or absent

fourth pharyngeal arch artery hypoplasia ( J:110378 )

• hypoplastic at E10.5

abnormal aortic arch morphology ( J:188772 )

retroesophageal right subclavian artery ( J:188772 )

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all heterozygotes exhibit at least one abnormal fourth pharyngeal arch artery (PAA), that is typically scored as abnormally small or absent

fourth pharyngeal arch artery hypoplasia ( J:110378 )

• hypoplastic at E10.5

abnormal palate morphology ( J:188772 )

embryo

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• at E10.5, all heterozygotes exhibit at least one abnormal fourth pharyngeal arch artery (PAA), that is typically scored as abnormally small or absent

fourth pharyngeal arch artery hypoplasia ( J:110378 )

• hypoplastic at E10.5

digestive/alimentary system

abnormal palate morphology ( J:188772 )

growth/size/body

abnormal palate morphology ( J:188772 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:67409

Genotype
MGI:7543764

ht7

• Allelic Composition: Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

mortality/aging ( J:314464 )

N • heterozygotes are recovered at normal Mendelian ratios at E14.5

cardiovascular system

abnormal right subclavian artery morphology ( J:314464 )

• at E14.5, 8% of heterozygotes exhibit an aberrant right subclavian artery

abnormal cardiac outflow tract development ( J:314464 )

• at E14.5, 8% of heterozygotes show OFT rotational defects

• however, no common arterial trunk is identified at E14.5

perimembraneous ventricular septal defect ( J:314464 )

• at E14.5, 31% of heterozygotes exhibit a perimembranous VSD

Genotype
MGI:5583879

ht8

• Allelic Composition: Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

cardiovascular system

abnormal blood vessel morphology ( J:212881 )

• 41% of E11.5 embryos show aplastic vessels while 31% of E11.5 embryos show hypoplastic vessels

• 53% of E12.5 embryos show vessel defects, including patent right carotid duct, with 37% presenting aplastic vessels

• 46% of E13.5 embryos show fourth-related abnormal great vessel configurations

• 29% of embryos show great vessel anomalies at E15.5

abnormal artery development ( J:212881 )

• increase in numbers of apoptotic cells surrounding both sixth arch arteries at E11.5

abnormal pharyngeal arch artery morphology ( J:212881 )

• 65% of E11.5 embryos exhibit arch artery defects, however by E15.5, mice recover from this defect such that only 29% of mice have arch artery abnormalities

abnormal fourth pharyngeal arch artery morphology ( J:212881 )

• 24% of embryos show aplastic fourth arch artery defects at E11.5

• 46% of E13.5 embryos show fourth-related abnormal great vessel configurations

vascular smooth muscle hypoplasia ( J:212881 )

• the number of SM22-positive cells (differentiated vascular smooth muscle cells) surrounding the 4th arch arteries are reduced at E10.5

• at E11.5, the vascular smooth muscle cell component is reduced in depth/thickness in the hypoplastic vessels, however discontinuities of vascular smooth muscle cell coverage are no longer observed

increased vascular smooth muscle cell proliferation ( J:212881 )

• increase in proliferation of vascular smooth muscle cells in the pharyngeal system at E10.5

craniofacial

abnormal pharyngeal arch artery morphology ( J:212881 )

• 65% of E11.5 embryos exhibit arch artery defects, however by E15.5, mice recover from this defect such that only 29% of mice have arch artery abnormalities

abnormal fourth pharyngeal arch artery morphology ( J:212881 )

• 24% of embryos show aplastic fourth arch artery defects at E11.5

• 46% of E13.5 embryos show fourth-related abnormal great vessel configurations

embryo

abnormal pharyngeal arch artery morphology ( J:212881 )

• 65% of E11.5 embryos exhibit arch artery defects, however by E15.5, mice recover from this defect such that only 29% of mice have arch artery abnormalities

abnormal fourth pharyngeal arch artery morphology ( J:212881 )

• 24% of embryos show aplastic fourth arch artery defects at E11.5

• 46% of E13.5 embryos show fourth-related abnormal great vessel configurations

muscle

vascular smooth muscle hypoplasia ( J:212881 )

• the number of SM22-positive cells (differentiated vascular smooth muscle cells) surrounding the 4th arch arteries are reduced at E10.5

• at E11.5, the vascular smooth muscle cell component is reduced in depth/thickness in the hypoplastic vessels, however discontinuities of vascular smooth muscle cell coverage are no longer observed

increased vascular smooth muscle cell proliferation ( J:212881 )

• increase in proliferation of vascular smooth muscle cells in the pharyngeal system at E10.5

cellular

increased vascular smooth muscle cell proliferation ( J:212881 )

• increase in proliferation of vascular smooth muscle cells in the pharyngeal system at E10.5

Genotype
MGI:3841292

ht9

• Allelic Composition: Tbx1^m1Jlk/Tbx1^tm1Bld
• Genetic Background: involves: 129

craniofacial

abnormal pharyngeal arch artery morphology ( J:146769 )

• dysmorphic aortic arch arteries

• 100% penetrance

cleft palate ( J:146769 )

• 50% penetrance

abnormal outer ear morphology ( J:146769 )

• malformed

• 60% penetrance

hematopoietic system

athymia ( J:146769 )

• 100% penetrance

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:146769 )

• dysmorphic aortic arch arteries

• 100% penetrance

persistent truncus arteriosus ( J:146769 )

• 100% penetrance

digestive/alimentary system

cleft palate ( J:146769 )

• 50% penetrance

hearing/vestibular/ear

abnormal outer ear morphology ( J:146769 )

• malformed

• 60% penetrance

immune system

athymia ( J:146769 )

• 100% penetrance

embryo

abnormal pharyngeal arch artery morphology ( J:146769 )

• dysmorphic aortic arch arteries

• 100% penetrance

endocrine/exocrine glands

athymia ( J:146769 )

• 100% penetrance

growth/size/body

cleft palate ( J:146769 )

• 50% penetrance

abnormal outer ear morphology ( J:146769 )

• malformed

• 60% penetrance

Genotype
MGI:5551756

ht10

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm6(cre)Bld
• Genetic Background: involves: 129S7/SvEvBrd

cardiovascular system

persistent truncus arteriosus ( J:204435 )

• in all mice

ventricular septal defect ( J:204435 )

• in all mice

Genotype
MGI:5140364

ht11

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm7.1Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

craniofacial

abnormal craniofacial development ( J:166754 )

• authors state that mice exhibit the same phenotype as Tbx1^tm1Bld heterozygotes

Genotype
MGI:3046798

ht12

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm2Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal heart development ( J:91013 )

• compound heterozygotes show the same cardiovascular phenotype as Tbx1^tm1Bld homozygotes

craniofacial

craniofacial phenotype ( J:91013 )

N • none of the mutants had cleft palates at E18.5 unlike Tbx1^tm1Bld homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:91013
velocardiofacial syndrome		DOID:12583	OMIM:192430	J:91013

Genotype
MGI:3641317

ht13

• Allelic Composition: Tbx1^tm1Bld/Tbx1^{tm1(Fgf8)Vite}
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

embryo

abnormal pharyngeal arch morphology ( J:110620 )

• at E10.5, embryos show an abnormal pharynx lacking caudal arches

absent pharyngeal arch arteries ( J:110620 )

• arch arteries are absent at E10.5

craniofacial

abnormal pharyngeal arch morphology ( J:110620 )

• at E10.5, embryos show an abnormal pharynx lacking caudal arches

absent pharyngeal arch arteries ( J:110620 )

• arch arteries are absent at E10.5

cardiovascular system

absent pharyngeal arch arteries ( J:110620 )

• arch arteries are absent at E10.5

double aortic arch ( J:110620 )

• one fetus had double aortic arch with aortic dilation

persistent truncus arteriosus ( J:110620 )

• PTA associated with the right or left aortic arch is observed at E18.5; in all affected mutants, PTA communicates solely with the right ventricle

abnormal interventricular septum morphology ( J:110620 )

• a ventricular septal defect is observed

abnormal semilunar valve morphology ( J:110620 )

• there is a loss of continuity between the mitral and semilunar valves

Genotype
MGI:3686780

ht14

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm5Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal cardiovascular system morphology ( J:112457 )

• embryos exhibit phenotypic abnormalities of the same type as those seen in Tbx1^tm1Bld homozygotes, although in some cases with a milder expressivity

abnormal pharyngeal arch artery morphology ( J:112457 )

absent fourth pharyngeal arch artery ( J:112457 )

• absent

absent sixth pharyngeal arch artery ( J:112457 )

• the 3rd and/or 6th pharyngeal arch arteries are missing in one or both sides

absent third pharyngeal arch artery ( J:112457 )

• the 3rd and/or 6th pharyngeal arch arteries are missing in one or both sides

abnormal aortic arch morphology ( J:112457 )

• aortic arch defects

persistent truncus arteriosus ( J:112457 )

ventricular septal defect ( J:112457 )

• exhibit a ventricular septal defect

craniofacial

abnormal pharyngeal arch artery morphology ( J:112457 )

absent fourth pharyngeal arch artery ( J:112457 )

• absent

abnormal fourth pharyngeal arch morphology ( J:112457 )

• lacks segmentation

small second pharyngeal arch ( J:112457 )

• exhibit variable severity of 2nd pharyngeal arch hypoplasia the 3rd, 4th, and 6th pharyngeal arches are not segmented

abnormal sixth pharyngeal arch morphology ( J:112457 )

• lacks segmentation

absent sixth pharyngeal arch artery ( J:112457 )

• the 3rd and/or 6th pharyngeal arch arteries are missing in one or both sides

abnormal third pharyngeal arch morphology ( J:112457 )

• lacks segmentation

absent third pharyngeal arch artery ( J:112457 )

• the 3rd and/or 6th pharyngeal arch arteries are missing in one or both sides

ear lobe hypoplasia ( J:112457 )

• exhibit variable severity of external ear hypoplasia

embryo

abnormal pharyngeal arch artery morphology ( J:112457 )

absent fourth pharyngeal arch artery ( J:112457 )

• absent

abnormal fourth pharyngeal arch morphology ( J:112457 )

• lacks segmentation

small second pharyngeal arch ( J:112457 )

• exhibit variable severity of 2nd pharyngeal arch hypoplasia the 3rd, 4th, and 6th pharyngeal arches are not segmented

abnormal sixth pharyngeal arch morphology ( J:112457 )

• lacks segmentation

absent sixth pharyngeal arch artery ( J:112457 )

• the 3rd and/or 6th pharyngeal arch arteries are missing in one or both sides

abnormal third pharyngeal arch morphology ( J:112457 )

• lacks segmentation

absent third pharyngeal arch artery ( J:112457 )

• the 3rd and/or 6th pharyngeal arch arteries are missing in one or both sides

hearing/vestibular/ear

ear lobe hypoplasia ( J:112457 )

• exhibit variable severity of external ear hypoplasia

hematopoietic system

athymia ( J:112457 )

• no thymus is seen except for 3 embryos that show severe hypoplasia

immune system

athymia ( J:112457 )

• no thymus is seen except for 3 embryos that show severe hypoplasia

respiratory system

pharynx hypoplasia ( J:112457 )

endocrine/exocrine glands

athymia ( J:112457 )

• no thymus is seen except for 3 embryos that show severe hypoplasia

growth/size/body

ear lobe hypoplasia ( J:112457 )

• exhibit variable severity of external ear hypoplasia

Genotype
MGI:5140381

ht15

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm8.1Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

craniofacial

abnormal craniofacial development ( J:166754 )

• authors state that mice exhibit the same phenotype as Tbx1^tm1Bld heterozygotes

Genotype
MGI:4410378

cn16

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm2.1Bem; Tfap2a^tm1(cre)Moon/Tfap2a⁺
• Genetic Background: either: (involves: 129/Sv * C57BL/6 * SJL) or (involves: 129/Sv * C57BL/6J * CBA * SJL)

cardiovascular system

abnormal aortic arch morphology ( J:154590 )

• in 9 of 20 mice

aberrant origin of the right subclavian artery ( J:154590 )

• at E15.5, 11 of 20 mice exhibit aberrant right subclavian artery unlike wild-type mice

abnormal cardiac outflow tract development ( J:154590 )

• mice exhibit defects in the great vessels unlike wild-type mice

persistent truncus arteriosus ( J:154590 )

• one mouse exhibits truncus arteriosus communis unlike wild-type mice

ventricular septal defect ( J:154590 )

• at E15.5 in one mouse

• at E18.5 in one mouse

craniofacial

cleft palate ( J:154590 )

• in 9 of 20 mice

immune system

thymus hypoplasia ( J:154590 )

• 12 of 20 mice exhibit an absent or hypoplastic thymus unlike wild-type mice

athymia ( J:154590 )

• 12 of 20 mice exhibit an absent or hypoplastic thymus unlike wild-type mice

digestive/alimentary system

cleft palate ( J:154590 )

• in 9 of 20 mice

hematopoietic system

thymus hypoplasia ( J:154590 )

• 12 of 20 mice exhibit an absent or hypoplastic thymus unlike wild-type mice

athymia ( J:154590 )

• 12 of 20 mice exhibit an absent or hypoplastic thymus unlike wild-type mice

endocrine/exocrine glands

thymus hypoplasia ( J:154590 )

• 12 of 20 mice exhibit an absent or hypoplastic thymus unlike wild-type mice

athymia ( J:154590 )

• 12 of 20 mice exhibit an absent or hypoplastic thymus unlike wild-type mice

growth/size/body

cleft palate ( J:154590 )

• in 9 of 20 mice

Genotype
MGI:3046801

cn17

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm3Bld; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal aortic arch morphology ( J:91013 )

• at E18.5 only those aortic arch abnormalities present in Tbx1^tm1Bld heterozygotes are seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:91013

Genotype
MGI:3046805

cn18

• Allelic Composition: Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺; Tbx1^tm1Bld/Tbx1^tm3Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:91013 )

• the aortic arch abnormalities are milder than those present in Tbx1^tm1Bld homozygotes as the 3rd and 6th pharyngeal arch artery form and develop normally while the 4th pharyngeal arch artery is absent or hypoplastic

absent fourth pharyngeal arch artery ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

fourth pharyngeal arch artery hypoplasia ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

persistent truncus arteriosus ( J:91013 )

• the same cardiovascular phenotype as in Tbx1^tm1Bld homozygotes is seen including truncus arteriosus

cellular

decreased mitotic index ( J:91013 )

• the mitotic index in the secondary heart field and adjacent splanchnic mesoderm is reduced by 18% and 19%, respectively

craniofacial

craniofacial phenotype ( J:91013 )

N • none of the mutants had cleft palates at E18.5 unlike Tbx1^tm1Bld homozygotes

abnormal pharyngeal arch artery morphology ( J:91013 )

• the aortic arch abnormalities are milder than those present in Tbx1^tm1Bld homozygotes as the 3rd and 6th pharyngeal arch artery form and develop normally while the 4th pharyngeal arch artery is absent or hypoplastic

absent fourth pharyngeal arch artery ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

fourth pharyngeal arch artery hypoplasia ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

immune system

small thymus ( J:91013 )

• the thymus is present but smaller than normal with widely separated lobes

embryo

abnormal pharyngeal arch artery morphology ( J:91013 )

• the aortic arch abnormalities are milder than those present in Tbx1^tm1Bld homozygotes as the 3rd and 6th pharyngeal arch artery form and develop normally while the 4th pharyngeal arch artery is absent or hypoplastic

absent fourth pharyngeal arch artery ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

fourth pharyngeal arch artery hypoplasia ( J:91013 )

• the 4th pharyngeal arch artery is absent or hypoplastic

hematopoietic system

small thymus ( J:91013 )

• the thymus is present but smaller than normal with widely separated lobes

endocrine/exocrine glands

small thymus ( J:91013 )

• the thymus is present but smaller than normal with widely separated lobes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:91013

Genotype
MGI:3046803

cn19

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm3Bld; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

abnormal aortic arch morphology ( J:91013 )

• at E18.5 only those aortic arch abnormalities present in Tbx1^tm1Bld heterozygotes are seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:91013

Genotype
MGI:3641322

cn20

• Allelic Composition: Hoxa3^tm1(cre)Moon/Hoxa3⁺; Tbx1^tm3Bld/Tbx1^tm1Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

persistent truncus arteriosus ( J:110620 )

• at E18.5 embryos are found to display PTA

Genotype
MGI:4453459

cn21

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm3Bld; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

immune system

abnormal lymphatic vessel morphology ( J:159824 )

• at E13.5 and E18.5, mice treated with tamoxifen at E11.5 and E12.5 lack identifiable mesenteric lymphatic vessels unlike in wild-type mice

• however, normal lymphatic vessel development occurs when mice are treated with tamoxifen at E14.5

abnormal lymphangiogenesis ( J:159824 )

• at E13.5 and E18.5, mice treated with tamoxifen at E11.5 and E12.5 lack identifiable mesenteric lymphatic vessels unlike in wild-type mice

• however, normal lymphatic vessel development occurs when mice are treated with tamoxifen at E14.5

Genotype
MGI:3686782

cn22

• Allelic Composition: Mesp1^tm2(cre)Ysa/Mesp1⁺; Tbx1^tm1Bld/Tbx1^tm5Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

cardiovascular system

cardiovascular system phenotype ( J:112457 )

N • exhibit rescue of the outflow tract defects, the formation and remodeling of the 3rd and 6th pharyngeal arch arteries and the hypoplasia of the 2nd pharyngeal arch

absent fourth pharyngeal arch artery ( J:112457 )

• exhibit 4th pharyngeal arch artery aplasia

• however, formation and remodeling of the 3rd and 6th pharyngeal arch arteries is rescued

craniofacial

absent fourth pharyngeal arch artery ( J:112457 )

• exhibit 4th pharyngeal arch artery aplasia

• however, formation and remodeling of the 3rd and 6th pharyngeal arch arteries is rescued

absent fourth pharyngeal arch ( J:112457 )

• exhibit 4th pharyngeal arch aplasia

• however exhibit rescue of the 2nd arch hypoplasia

embryo

absent fourth pharyngeal arch artery ( J:112457 )

• exhibit 4th pharyngeal arch artery aplasia

• however, formation and remodeling of the 3rd and 6th pharyngeal arch arteries is rescued

abnormal neural crest cell migration ( J:112457 )

• the neural crest migration and cranial nerve pathway abnormalities are only marginally improved

absent fourth pharyngeal arch ( J:112457 )

• exhibit 4th pharyngeal arch aplasia

• however exhibit rescue of the 2nd arch hypoplasia

hematopoietic system

athymia ( J:112457 )

• absent at E18.5

immune system

athymia ( J:112457 )

• absent at E18.5

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:112457 )

N • exhbiit rescue of the external ear hypolasia

cellular

abnormal neural crest cell migration ( J:112457 )

• the neural crest migration and cranial nerve pathway abnormalities are only marginally improved

endocrine/exocrine glands

athymia ( J:112457 )

• absent at E18.5

Genotype
MGI:3686776

cn23

• Allelic Composition: Mesp1^tm2(cre)Ysa/Mesp1⁺; Tbx1^tm1Bld/Tbx1^tm3Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

cardiovascular system

abnormal pharyngeal arch artery morphology ( J:112457 )

absent fourth pharyngeal arch artery ( J:112457 )

• absent at E10.5

absent sixth pharyngeal arch artery ( J:112457 )

• absent at E10.5

absent third pharyngeal arch artery ( J:112457 )

• absent at E10.5

abnormal aortic arch morphology ( J:112457 )

• 100% show aortic arch defects

abnormal cardiac outflow tract development ( J:112457 )

persistent truncus arteriosus ( J:112457 )

• 100% penetrance

abnormal interventricular septum morphology ( J:112457 )

• 100% penetrance of ventricular septal defect

embryo

abnormal cardiac neural crest cell migration ( J:112457 )

• the post-otic stream directed to the 3rd pharyngeal arch is interrupted and the circumpharyngeal stream is abnormally distributed

abnormal cranial neural crest cell migration ( J:112457 )

• the pre-otic stream on neural crest cells directed to the 2nd pharyngeal arch is reduced

abnormal pharyngeal arch morphology ( J:112457 )

abnormal pharyngeal arch artery morphology ( J:112457 )

absent fourth pharyngeal arch artery ( J:112457 )

• absent at E10.5

absent sixth pharyngeal arch artery ( J:112457 )

• absent at E10.5

absent third pharyngeal arch artery ( J:112457 )

• absent at E10.5

absent fourth pharyngeal arch ( J:112457 )

• exhibit loss of the 4th pharyngeal arch at E10.5

second pharyngeal arch hypoplasia ( J:112457 )

• exhibit hypoplasia of the 2nd pharyngeal arch at E10.5

absent sixth pharyngeal arch ( J:112457 )

• exhibit loss of the 6th pharyngeal arch at E10.5

absent third pharyngeal arch ( J:112457 )

• exhibit loss of the 3rd pharyngeal arch at E10.5

abnormal mesenchyme morphology ( J:112457 )

• exhibit reduced proliferation of mesenchymal cells at E8.5

abnormal fourth pharyngeal pouch morphology ( J:112457 )

• the 4th pouch is smaller

hearing/vestibular/ear

ear lobe hypoplasia ( J:112457 )

• 100% show hypoplastic external ears

hematopoietic system

thymus hypoplasia ( J:112457 )

• 3 of 15 show thymic hypoplasia

athymia ( J:112457 )

• 12 of 15 show thymic aplasia

nervous system

abnormal accessory nerve morphology ( J:112457 )

• terminal projections of the accessory nerve show disarray and are fused with each other

glossopharyngeal nerve hypoplasia ( J:112457 )

• glossopharyngeal nerve is hypoplastic and the terminal projections show disarray and are fused with each other

abnormal mandibular nerve branching ( J:112457 )

• the mandibular branch of the trigeminal nerve is fused caudally with the facial nerve

abnormal vagus nerve morphology ( J:112457 )

• terminal projections of the vagus nerve show disarray and are fused with each other

respiratory system

pharynx hypoplasia ( J:112457 )

• severe

craniofacial

craniofacial phenotype ( J:112457 )

N • do not exhibit cleft palate

abnormal pharyngeal arch morphology ( J:112457 )

abnormal pharyngeal arch artery morphology ( J:112457 )

absent fourth pharyngeal arch artery ( J:112457 )

• absent at E10.5

absent sixth pharyngeal arch artery ( J:112457 )

• absent at E10.5

absent third pharyngeal arch artery ( J:112457 )

• absent at E10.5

absent fourth pharyngeal arch ( J:112457 )

• exhibit loss of the 4th pharyngeal arch at E10.5

second pharyngeal arch hypoplasia ( J:112457 )

• exhibit hypoplasia of the 2nd pharyngeal arch at E10.5

absent sixth pharyngeal arch ( J:112457 )

• exhibit loss of the 6th pharyngeal arch at E10.5

absent third pharyngeal arch ( J:112457 )

• exhibit loss of the 3rd pharyngeal arch at E10.5

ear lobe hypoplasia ( J:112457 )

• 100% show hypoplastic external ears

immune system

thymus hypoplasia ( J:112457 )

• 3 of 15 show thymic hypoplasia

athymia ( J:112457 )

• 12 of 15 show thymic aplasia

cellular

abnormal cardiac neural crest cell migration ( J:112457 )

• the post-otic stream directed to the 3rd pharyngeal arch is interrupted and the circumpharyngeal stream is abnormally distributed

abnormal cranial neural crest cell migration ( J:112457 )

• the pre-otic stream on neural crest cells directed to the 2nd pharyngeal arch is reduced

endocrine/exocrine glands

thymus hypoplasia ( J:112457 )

• 3 of 15 show thymic hypoplasia

athymia ( J:112457 )

• 12 of 15 show thymic aplasia

growth/size/body

ear lobe hypoplasia ( J:112457 )

• 100% show hypoplastic external ears

Genotype
MGI:7543763

cn24

• Allelic Composition: Setd5^{tm1c(EUCOMM)Wtsi}/Setd5⁺; Tbx1^tm1Bld/Tbx1⁺; Tmem163^{Tg(ACTB-cre)2Mrt}/Tmem163⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB/N

mortality/aging

mortality/aging ( J:314464 )

N • double heterozygotes are recovered at normal Mendelian ratios at E14.5

cardiovascular system

abnormal right subclavian artery morphology ( J:314464 )

• at E14.5, 21% of double heterozygotes exhibit an aberrant right subclavian artery

abnormal cardiac outflow tract development ( J:314464 )

• at E14.5, 57% of double heterozygotes show OFT rotational defects, including DORV and overriding aorta

• however, no common arterial trunk is identified at E14.5

double outlet right ventricle ( J:314464 )

overriding aortic valve ( J:314464 )

perimembraneous ventricular septal defect ( J:314464 )

• at E14.5, 86% of double heterozygotes exhibit a perimembranous VSD

Genotype
MGI:5551755

cn25

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Tbx1/GFP)Bem}/Gt(ROSA)26Sor^{tm1(Tbx1/GFP)Bem}; Tbx1^tm1Bld/Tbx1^tm6(cre)Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

Gt(ROSA)26Sor^{tm1(Tbx1/GFP)Bem} can patially rescue heart phenotypes in Tbx1^tm6(cre)Bld/Tbx1^tm1Bld mice

cardiovascular system

persistent truncus arteriosus ( J:204435 )

• in 5 of 6 mice

double outlet right ventricle ( J:204435 )

• in 1 of 6 mice

ventricular septal defect ( J:204435 )

• in 5 of 6 mice

Genotype
MGI:5551754

cn26

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Tbx1/GFP)Bem}/Gt(ROSA)26Sor⁺; Tbx1^tm1Bld/Tbx1^tm6(cre)Bld
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

Failure of inner ear morphogenesis in Tbx1^tm1Bld/Tbx1^tm1Bld mice at E14.5 and partial rescue of inner ear morphogenesis in Tbx1^tm6(cre)Bld/Tbx1^tm1Bld Gt(ROSA)26Sor^{tm1(Tbx1/GFP)Bem}/ Gt(ROSA)26Sor⁺ mice

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:204435 )

N • recovery of the anterior and posterior semicircular canals compared with null mice

abnormal cochlea morphology ( J:204435 )

• partial rescue with null mice

abnormal vestibular saccule morphology ( J:204435 )

• partial rescue with null mice

cardiovascular system

double outlet right ventricle ( J:204435 )

• in half of mice

ventricular septal defect ( J:204435 )

• in all mice

Genotype
MGI:4453460

cn27

• Allelic Composition: Tbx1^tm1Bld/Tbx1^tm3Bld; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:159824 )

• mice die between P2 and P4

immune system

abnormal lymphatic vessel morphology ( J:159824 )

• at E18.5, mice lack mesenteric lymph vessels unlike wild-type mice

abnormal lymphangiogenesis ( J:159824 )

• development of gastrointestinal lymphatic vasculature fails unlike in wild-type mice

homeostasis/metabolism

dehydration ( J:159824 )

• between P2 and P4

chylous ascites ( J:159824 )

• between P2 and P4, mice exhibit abdominal chylous ascites unlike wild-type mice

growth/size/body

postnatal growth retardation ( J:159824 )

Genotype
MGI:4410367

cx28

• Allelic Composition: Chd7^Whi/Chd7⁺; Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: B6.Cg-Chd7^Whi Tbx1^tm1Bld

Malformations of the semicircular canals in Chd7^Whi/Chd7⁺, Tbx1^tm1Bld/Tbx1⁺, and Chd7^Whi/Chd7⁺ Tbx1^tm1Bld/Tbx1⁺ mice

hearing/vestibular/ear

abnormal lateral semicircular canal morphology ( J:154590 )

• all mice exhibit defects in the lateral canal including canal truncation (16%), presence of only the ampulla (67%), or absence of the canal (17%) unlike wild-type mice

absent lateral semicircular canal ( J:154590 )

• in 17% of mice

abnormal posterior semicircular canal morphology ( J:154590 )

• 58% mice exhibit posterior canal truncations unlike wild-type mice

• 42% of mice exhibit posterior canal fused to the crus commune unlike wild-type mice

Genotype
MGI:4410364

cx29

• Allelic Composition: Chd7^Gt(XK403)Byg/Chd7⁺; Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: either: (involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6) or (involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * CD-1)

Pharyngeal arch artery patterning defects in Chd7^Whi/Chd7⁺, Chd7^Gt(XK403)Byg/Chd7⁺ and Chd7^Gt(XK403)Byg/Chd7⁺ Tbx1^tm1Bld/Tbx1⁺ embryos

cardiovascular system

absent fourth pharyngeal arch artery ( J:154590 )

• at E10.5, 6 of 17 mice exhibit bilateral fourth pharyngeal arch aplasia compared with 1 of 9 single heterozygotes

interrupted aortic arch ( J:154590 )

• at E14.5, mice exhibit an increase in interrupted aortic arches compared with either single heterozygote

abnormal subclavian artery morphology ( J:154590 )

• at E14.5, 7 of 17 mice exhibit aberrant right subclavian artery unlike wild-type mice

craniofacial

absent fourth pharyngeal arch artery ( J:154590 )

• at E10.5, 6 of 17 mice exhibit bilateral fourth pharyngeal arch aplasia compared with 1 of 9 single heterozygotes

embryo

absent fourth pharyngeal arch artery ( J:154590 )

• at E10.5, 6 of 17 mice exhibit bilateral fourth pharyngeal arch aplasia compared with 1 of 9 single heterozygotes

hearing/vestibular/ear

abnormal ear development ( J:154590 )

hematopoietic system

ectopic thymus ( J:154590 )

• at E14.5, 4 of 17 mice exhibit ectopic thymus gland unlike single heterozygotes

immune system

ectopic thymus ( J:154590 )

• at E14.5, 4 of 17 mice exhibit ectopic thymus gland unlike single heterozygotes

endocrine/exocrine glands

ectopic thymus ( J:154590 )

• at E14.5, 4 of 17 mice exhibit ectopic thymus gland unlike single heterozygotes

Genotype
MGI:5447056

cx30

• Allelic Composition: Kat6a^tm1Avo/Kat6a⁺; Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129 * 129S7/SvEvBrd * BALB/c * C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:188772 )

• 80% of expected mice die before weaning

cardiovascular system

abnormal cardiovascular system morphology ( J:188772 )

• more mice exhibit DiGeorge-like symptoms compared with single heterozygotes

craniofacial

abnormal craniofacial morphology ( J:188772 )

• more mice exhibit DiGeorge-like symptoms compared with single heterozygotes

skeleton

abnormal skeleton morphology ( J:188772 )

• more mice exhibit DiGeorge-like symptoms compared with single heterozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:188772

Genotype
MGI:3611260

cx31

• Allelic Composition: Fgf8^tm1.4Mrt/Fgf8⁺; Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * ICR

cardiovascular system

abnormal fourth pharyngeal arch artery morphology ( J:78686 )

• all aortic arch patterning defects observed at E18.5 are attributable to a failure of the fourth pharyngeal arch artery (PAA) development evident at E10.5; the third and sixth PAAs appear normal

• the number of arteries scored as non-patent to ink (i.e. 'absent' fourth PAA) are significantly higher in double heterozygotes than in embryos heterozygous for Tbx1^tm1Bld alone

abnormal aortic arch morphology ( J:78686 )

abnormal aortic arch development ( J:78686 )

• at E18.5, 18 out of 36 (50%) of double heterozygotes exhibit aortic arch patterning defects vs 27% of mice heterozygous for Tbx1^tm1Bld alone

cervical aortic arch ( J:78686 )

• three show A-RSA associated with a cervical aortic arch

interrupted aortic arch, type b ( J:78686 )

• eight of these 18 double heterozygotes exhibit interruption of the aortic arch type B (IAA-B, occurring between the left common carotid artery and the left subclavian artery) associated with a right aortic arch (RAA)

right aortic arch ( J:78686 )

• eight of these 18 double heterozygotes exhibit interruption of the aortic arch type B (IAA-B, occurring between the left common carotid artery and the left subclavian artery) associated with a right aortic arch (RAA)

immune system

thymus hypoplasia ( J:78686 )

• at E18.5, 14 of 30 double heterozygotes exhibit thymic hypoplasia and/or lobe asymmetry

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:78686 )

• all aortic arch patterning defects observed at E18.5 are attributable to a failure of the fourth pharyngeal arch artery (PAA) development evident at E10.5; the third and sixth PAAs appear normal

• the number of arteries scored as non-patent to ink (i.e. 'absent' fourth PAA) are significantly higher in double heterozygotes than in embryos heterozygous for Tbx1^tm1Bld alone

embryo

abnormal fourth pharyngeal arch artery morphology ( J:78686 )

• all aortic arch patterning defects observed at E18.5 are attributable to a failure of the fourth pharyngeal arch artery (PAA) development evident at E10.5; the third and sixth PAAs appear normal

• the number of arteries scored as non-patent to ink (i.e. 'absent' fourth PAA) are significantly higher in double heterozygotes than in embryos heterozygous for Tbx1^tm1Bld alone

hematopoietic system

thymus hypoplasia ( J:78686 )

• at E18.5, 14 of 30 double heterozygotes exhibit thymic hypoplasia and/or lobe asymmetry

endocrine/exocrine glands

thymus hypoplasia ( J:78686 )

• at E18.5, 14 of 30 double heterozygotes exhibit thymic hypoplasia and/or lobe asymmetry

Genotype
MGI:5583877

cx32

• Allelic Composition: Smad7^{Gt(YHC053)Byg}/Smad7⁺; Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6J

cardiovascular system

abnormal artery development ( J:212881 )

• increase in numbers of apoptotic cells surrounding both sixth arch arteries at E11.5

abnormal pharyngeal arch artery morphology ( J:212881 )

• 63% of E11.5 embryos exhibit arch artery defects, however unlike single Tbx1 heterozygotes, double mutants do not recover from these defects at E15.5 and 68% show arch artery defects at this time

• hypoplastic vessels have a smaller cross-sectional area than single Tbx1 heterozygotes, and some show irregular lumen shapes

abnormal fourth pharyngeal arch artery morphology ( J:212881 )

• 38% of embryos exhibit aplastic fourth arch artery defects at E11.5

• abnormal extracellular matrix deposition/organization of the fourth arch arteries

vascular smooth muscle hypoplasia ( J:212881 )

• the number of SM22-positive cells (differentiated vascular smooth muscle cells) surrounding the 4th arch arteries are reduced compared to single Tbx1 heterozygotes at E10.5

• at E11.5, the vascular smooth muscle cell component is reduced in depth/thickness in the hypoplastic vessels, however discontinuities of vascular smooth muscle cell coverage are no longer observed

increased vascular smooth muscle cell proliferation ( J:212881 )

• increase in proliferation of vascular smooth muscle cells in the pharyngeal system at E10.5

craniofacial

abnormal pharyngeal arch artery morphology ( J:212881 )

• 63% of E11.5 embryos exhibit arch artery defects, however unlike single Tbx1 heterozygotes, double mutants do not recover from these defects at E15.5 and 68% show arch artery defects at this time

• hypoplastic vessels have a smaller cross-sectional area than single Tbx1 heterozygotes, and some show irregular lumen shapes

abnormal fourth pharyngeal arch artery morphology ( J:212881 )

• 38% of embryos exhibit aplastic fourth arch artery defects at E11.5

• abnormal extracellular matrix deposition/organization of the fourth arch arteries

embryo

abnormal pharyngeal arch artery morphology ( J:212881 )

• 63% of E11.5 embryos exhibit arch artery defects, however unlike single Tbx1 heterozygotes, double mutants do not recover from these defects at E15.5 and 68% show arch artery defects at this time

• hypoplastic vessels have a smaller cross-sectional area than single Tbx1 heterozygotes, and some show irregular lumen shapes

abnormal fourth pharyngeal arch artery morphology ( J:212881 )

• 38% of embryos exhibit aplastic fourth arch artery defects at E11.5

• abnormal extracellular matrix deposition/organization of the fourth arch arteries

muscle

vascular smooth muscle hypoplasia ( J:212881 )

• the number of SM22-positive cells (differentiated vascular smooth muscle cells) surrounding the 4th arch arteries are reduced compared to single Tbx1 heterozygotes at E10.5

• at E11.5, the vascular smooth muscle cell component is reduced in depth/thickness in the hypoplastic vessels, however discontinuities of vascular smooth muscle cell coverage are no longer observed

increased vascular smooth muscle cell proliferation ( J:212881 )

• increase in proliferation of vascular smooth muscle cells in the pharyngeal system at E10.5

cellular

increased vascular smooth muscle cell proliferation ( J:212881 )

• increase in proliferation of vascular smooth muscle cells in the pharyngeal system at E10.5

Genotype
MGI:3639490

cx33

• Allelic Composition: Fgf15^tm1Sms/Fgf15⁺; Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6

cardiovascular system

abnormal aortic arch development ( J:97317 )

• at E18.5, double heterozygotes show no significant increase in the penetrance or severity of aortic arch patterning defects relative to Tbx1^tm1Bld heterozygotes

• observed defects include interrupted aortic arch type-B (20%), aberrant origin of the right subclavian artery (30%), and VSDs (membranous 20%; muscular: 10%)

aberrant origin of the right subclavian artery ( J:97317 )

interrupted aortic arch ( J:97317 )

perimembraneous ventricular septal defect ( J:97317 )

muscular ventricular septal defect ( J:97317 )

Genotype
MGI:3640192

cx34

• Allelic Composition: Tbx1^tm1Bld/Del(16Es2el-Ufd1l)217Bld
• Genetic Background: involves: 129S5/SvEvBrd * 129S7/SvEvBrd * C57BL/6

embryo

absent fourth pharyngeal arch artery ( J:67409 )

• absent

abnormal second pharyngeal arch artery morphology ( J:67409 )

• the second arch arteries are reduced in size

absent sixth pharyngeal arch artery ( J:67409 )

• absent

absent third pharyngeal arch artery ( J:67409 )

• absent

absent fourth pharyngeal arch ( J:67409 )

absent sixth pharyngeal arch ( J:67409 )

absent third pharyngeal arch ( J:67409 )

cardiovascular system

abnormal dorsal aorta morphology ( J:67409 )

• dorsal aortae originate directly from the aortic sac

absent fourth pharyngeal arch artery ( J:67409 )

• absent

abnormal second pharyngeal arch artery morphology ( J:67409 )

• the second arch arteries are reduced in size

absent sixth pharyngeal arch artery ( J:67409 )

• absent

absent third pharyngeal arch artery ( J:67409 )

• absent

craniofacial

absent fourth pharyngeal arch artery ( J:67409 )

• absent

abnormal second pharyngeal arch artery morphology ( J:67409 )

• the second arch arteries are reduced in size

absent sixth pharyngeal arch artery ( J:67409 )

• absent

absent third pharyngeal arch artery ( J:67409 )

• absent

absent fourth pharyngeal arch ( J:67409 )

absent sixth pharyngeal arch ( J:67409 )

absent third pharyngeal arch ( J:67409 )

Genotype
MGI:3713495

cx35

• Allelic Composition: Tbx1^tm1Bld/Del(16Es2el-Ufd1l)217Bld
• Genetic Background: involves: 129S7/SvEvBrd

cardiovascular system

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

abnormal sixth pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

abnormal third pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

abnormal sixth pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

abnormal third pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

small second pharyngeal arch ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

embryo

abnormal fourth pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

abnormal sixth pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

abnormal third pharyngeal arch artery morphology ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

small second pharyngeal arch ( J:67409 )

• identical phenotype to Tbx1^tm1Bld homozygotes

Genotype
MGI:5447057

cx36

• Allelic Composition: Kat6a^tm2.2Avo/Kat6a⁺; Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cardiovascular system

retroesophageal right subclavian artery ( J:188772 )

interrupted aortic arch, type b ( J:188772 )

ventricular septal defect ( J:188772 )

• large

craniofacial

cleft palate ( J:188772 )

hematopoietic system

small thymus ( J:188772 )

digestive/alimentary system

cleft palate ( J:188772 )

immune system

small thymus ( J:188772 )

endocrine/exocrine glands

small thymus ( J:188772 )

growth/size/body

cleft palate ( J:188772 )