Phenotypes Associated with This Genotype

Genotype
MGI:3698553

• Allelic Composition: Gbx2^tm1.1Mrt/Gbx2^tm1.1Mrt
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Swiss Webster

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

hearing/vestibular/ear

small otic vesicle ( J:98487 )

• at E9 to E9.5, some homozygotes display a reduced otocyst size

abnormal inner ear morphology ( J:98487 )

• at E15.5, homozygotes display variable inner ear phenotypes divided into four categories, with increasing severity from Type I to IV

• Type I homozygotes exhibit an enlarged membranous labyrinth which lacks the endolymphatic duct in 3/4 cases

• Type II homozygotes show absence of both the endolymphatic duct (7/7) and common crus (5/7); the utricle and saccule are not easily discernible, and the cochlear duct is shortened

• Type III homozygotes lack the anterior and posterior canals and show less than one coil, in addition to phenotypes described for Type II

• Type IV homozygotes display a cystic inner ear with only a lateral canal and ampulla in 3/5 cases

• in 8 of 10 cases, the two ears of a given specimen usually display similar phenotypes

inner ear cyst ( J:98487 )

• Type IV (i.e most severely affected) homozygotes exhibit cystic inner ears without any discernible structures except for the presence of a lateral canal in some cases (3/5)

abnormal cochlear sensory epithelium morphology ( J:98487 )

decreased cochlea coiling ( J:98487 )

• at E15.5, Type III homozygotes exhibit less than one coil

absent common crus ( J:98487 )

• overall, 68% (13 of 19) homozygotes lack a common crus (that is, five Type II, three Type III and five Type IV mutants)

absent lateral semicircular canal ( J:98487 )

• overall, 11% (2 of 19) homozygotes lack a lateral canal and ampulla (only Type IV mutants)

absent posterior semicircular canal ( J:98487 )

• overall, 42% (8 of 19) homozygotes lack a posterior canal (that is, three Type III and five Type IV mutants)

• overall, 21% (4 of 19) homozygotes lack an anterior ampulla (that is, one Type III and three Type IV mutants)

abnormal crista ampullaris morphology ( J:98487 )

• at E15.5, anterior and posterior cristae are generally present, except in some of Type IV specimens

absent superior semicircular canal ( J:98487 )

• overall, 42% (8 of 19) homozygotes lack an anterior canal (that is, three Type III and five Type IV mutants)

• overall, 21% (4 of 19) homozygotes lack an anterior ampulla (that is, one Type III and three Type IV mutants)

abnormal membranous labyrinth morphology ( J:98487 )

• overall, 18 of 19 homozygous mutant inner ears display an enlarged membranous labyrinth at E15.5

abnormal organ of Corti morphology ( J:98487 )

• at E15.5, the organ of Corti is severely affected in most mutants, with only one or two small sensory patches even in Type II mice

absent scala media ( J:98487 )

• overall, 26% (5 of 19) homozygotes lack a cochlear duct (only Type IV mutants)

• absence of cochlear duct extension is evident by E11.5

abnormal vestibular saccular macula morphology ( J:98487 )

• at E15.5, the saccular maccula is severely affected in most mutants, with no discernible sensory patches even in Type II mice

absent vestibular saccule ( J:98487 )

• overall, 42% (8 of 19) homozygotes lack a saccule (that is, one Type I, one Type II, two Type III and four Type IV mutants)

absent endolymphatic duct ( J:98487 )

• overall, 95% (18 of 19) homozygous mutant inner ears lack an endolymphatic duct at E15.5

• absence of the endolymphatic duct is also noted at E11.5

nervous system

abnormal hindbrain development ( J:98487 )

• the anterior hindbrain rostral to r4 is missing and is replaced by an ill-defined zone with aberrant gene expression patterns

• in addition, development of the caudal hindbrain is disrupted, as shown by changes in gene expression patterns caudal to r3

abnormal rhombomere 5 morphology ( J:98487 )

• at E9 to E9.5, r5 is abnormal based on gene expression patterns

abnormal metencephalon morphology ( J:98487 )

• the anterior hindbrain rostral to r4 is missing and is replaced by an ill-defined zone with aberrant gene expression patterns

abnormal cochlear ganglion morphology ( J:98487 )

• at E15.5, the spiral ganglion is present in most Type II specimens (2/3) but missing in 2/2 Type IV specimens

• TUNEL analysis indicates elevated apoptosis in the cochleo-vestibular ganglion at E9.5-E10.5

absent cochlear ganglion ( J:98487 )

• missing in 2/2 Type IV specimens

embryo

abnormal rhombomere 5 morphology ( J:98487 )

• at E9 to E9.5, r5 is abnormal based on gene expression patterns

growth/size/body

inner ear cyst ( J:98487 )

• Type IV (i.e most severely affected) homozygotes exhibit cystic inner ears without any discernible structures except for the presence of a lateral canal in some cases (3/5)