Phenotypes Associated with This Genotype

Genotype
MGI:3663465

• Allelic Composition: Gbx2^tm1.1Mrt/Gbx2^tm1.1Mrt
• Genetic Background: B6.129-Gbx2^tm1.1Mrt

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

mortality/aging

neonatal lethality, complete penetrance ( J:100584 )

• homozygotes survive to birth, but die soon afterwards

cardiovascular system

abnormal cardiovascular system morphology ( J:100584 )

• ~39% of homozygotes exhibit cardiovascular defects that affect development of the fourth PAAs and proper alignment of the conus (not observed in wild-type or heterozygous mice)

abnormal fourth pharyngeal arch artery morphology ( J:100584 )

• at E10.5, homozygotes show absence (nonpatent to ink) or hypoplasia of the left, right, or both fourth PAAs, with infrequent loss of the left sixth PAA and persistence of the right sixth PAA and descening aorta

• however, no defects in the development of the third PAA are observed, and initial pharyngeal arch segmentation appears unaffected

• at E10.5, endothelial cells are poorly organized in the mutant fourth PAA

abnormal aortic arch morphology ( J:100584 )

retroesophageal right subclavian artery ( J:100584 )

• 21% of homozygotes with cardiac defects exhibit a retroesophageal right subclavian artery

interrupted aortic arch, type b ( J:100584 )

• 26% of homozygotes with cardiac defects show interrupted aortic arch (IAA) type B, whereby the segment between the left common carotid artery and left subclavian artery is absent

right aortic arch ( J:100584 )

• 37% of homozygotes with cardiac defects display right aortic arch (RAA) with a right ductus arteriosus and persistence of the right descending aorta

abnormal vascular endothelial cell differentiation ( J:100584 )

• at E10.5, homozygotes show poor organization of endothelial cells in the fourth PAA

double outlet right ventricle ( J:100584 )

• 16% of homozygotes with cardiac defects display a double outlet right ventricle

overriding aortic valve ( J:100584 )

• 16% of homozygotes with cardiac defects exhibit an overriding aorta

perimembraneous ventricular septal defect ( J:100584 )

• mutant hearts with an overriding aorta display a mebraneous septal defect

• however, no VSDs are present in hearts with isolated arterial remodeling defects (IAA, RAA)

craniofacial

abnormal fourth pharyngeal arch artery morphology ( J:100584 )

• at E10.5, endothelial cells are poorly organized in the mutant fourth PAA

• at E10.5, homozygotes show absence (nonpatent to ink) or hypoplasia of the left, right, or both fourth PAAs, with infrequent loss of the left sixth PAA and persistence of the right sixth PAA and descening aorta

• however, no defects in the development of the third PAA are observed, and initial pharyngeal arch segmentation appears unaffected

abnormal styloid process morphology ( J:100584 )

• at E18.5, homozygotes display ectopic fusion of the styloid process with the base of the incus

styloid process hypoplasia ( J:100584 )

• at E18.5, 2 of 5 homozygotes display a severely hypoplastic styloid process

fusion of middle ear ossicles ( J:100584 )

• at E18.5, homozygotes display ectopic fusion of the styloid process with the base of the incus

middle ear ossicle hypoplasia ( J:100584 )

• at E18.5, 2 of 5 homozygotes display severely hypoplastic middle ear components, including the incus and malleus, as well as the styloid process and the stapes

cleft palate ( J:100584 )

• homozygotes infrequently exhibit a cleft palate

embryo

abnormal fourth pharyngeal arch artery morphology ( J:100584 )

• at E10.5, homozygotes show absence (nonpatent to ink) or hypoplasia of the left, right, or both fourth PAAs, with infrequent loss of the left sixth PAA and persistence of the right sixth PAA and descening aorta

• however, no defects in the development of the third PAA are observed, and initial pharyngeal arch segmentation appears unaffected

• at E10.5, endothelial cells are poorly organized in the mutant fourth PAA

abnormal neural crest cell migration ( J:100584 )

• at E9-E9.5, 4 of 6 homozygotes show significantly reduced migrating NCCs, esp. post-otic NCCs entering caudal pharyngeal arches (region of developing fourth PAAs)

abnormal neural crest cell morphology ( J:100584 )

• fourth PAA defects precede smooth muscle cell differentiation

decreased neural crest cell number ( J:100584 )

• at E10.5, NCCs are underrepresented in the mutant fourth PAAs

homeostasis/metabolism

cyanosis ( J:100584 )

• homozygous mutant pups appear cyanotic at birth

nervous system

abnormal neural crest cell morphology ( J:100584 )

• fourth PAA defects precede smooth muscle cell differentiation

decreased neural crest cell number ( J:100584 )

• at E10.5, NCCs are underrepresented in the mutant fourth PAAs

abnormal cerebellum morphology ( J:100584 )

• all homozygotes display cerebellar defects similar to those described in J:42110

abnormal innervation ( J:100584 )

• at E10.5, most homozygotes show ectopic projections between the trigeminal and the facial nerves

abnormal trigeminal ganglion morphology ( J:100584 )

• the mutant trigeminal ganglion is shifted ventrally directly behind the eye

fusion of glossopharyngeal and vagus nerve ( J:100584 )

• at E10.5, 3 of 4 homozygotes display fusion of the 9th (glossopharyngeal) and 10th (vagus) cranial nerves, just posterior to the otocyst

absent trigeminal nerve ( J:100584 )

hearing/vestibular/ear

fusion of middle ear ossicles ( J:100584 )

• at E18.5, homozygotes display ectopic fusion of the styloid process with the base of the incus

middle ear ossicle hypoplasia ( J:100584 )

• at E18.5, 2 of 5 homozygotes display severely hypoplastic middle ear components, including the incus and malleus, as well as the styloid process and the stapes

otic capsule hypoplasia ( J:100584 )

• at E18.5, all homozygotes exhibit a severely hypoplastic otic capsule

skeleton

abnormal styloid process morphology ( J:100584 )

• at E18.5, homozygotes display ectopic fusion of the styloid process with the base of the incus

styloid process hypoplasia ( J:100584 )

• at E18.5, 2 of 5 homozygotes display a severely hypoplastic styloid process

fusion of middle ear ossicles ( J:100584 )

• at E18.5, homozygotes display ectopic fusion of the styloid process with the base of the incus

middle ear ossicle hypoplasia ( J:100584 )

• at E18.5, 2 of 5 homozygotes display severely hypoplastic middle ear components, including the incus and malleus, as well as the styloid process and the stapes

digestive/alimentary system

cleft palate ( J:100584 )

• homozygotes infrequently exhibit a cleft palate

cellular

abnormal vascular endothelial cell differentiation ( J:100584 )

• at E10.5, homozygotes show poor organization of endothelial cells in the fourth PAA

abnormal neural crest cell migration ( J:100584 )

• at E9-E9.5, 4 of 6 homozygotes show significantly reduced migrating NCCs, esp. post-otic NCCs entering caudal pharyngeal arches (region of developing fourth PAAs)

growth/size/body

cleft palate ( J:100584 )

• homozygotes infrequently exhibit a cleft palate