Phenotypes associated with this allele

• Allele Symbol: Gfi1^tm1Sho
• Allele Name: targeted mutation 1, Stuart Orkin
• Allele ID: MGI:2449921
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gfi1^tm1Sho/Gfi1^tm1Sho	involves: 129S1/Sv * C57BL/6J	MGI:3696819
cx2	Atoh1^tm2Hzo/Atoh1^+ Gfi1^tm1Sho/Gfi1^tm1Sho	involves: 129S1/Sv * C57BL/6J	MGI:3696821

Genotype
MGI:3696819

hm1

• Allelic Composition: Gfi1^tm1Sho/Gfi1^tm1Sho
• Genetic Background: involves: 129S1/Sv * C57BL/6J

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

mortality/aging

premature death ( J:80025 )

• homozygotes survive for 3-6 months

growth/size/body

decreased body size ( J:80025 )

postnatal growth retardation ( J:80025 )

• by P10, homozygotes exhibit a reduced growth rate relative to wild-type littermates

• postnatal growth retardation increases in severity with age

behavior/neurological

absent startle reflex ( J:80025 )

• homozygotes lack a proper startle response to loud noises

ataxia ( J:80025 )

• by p10, homozygotes display an ataxic behavior which increases in severity with age

head tilt ( J:80025 )

hyperactivity ( J:80025 )

circling ( J:80025 )

hearing/vestibular/ear

abnormal cochlear hair cell morphology ( J:80025 )

• at E18.5, homozygotes display disorganized hair cells in the organ of Corti

abnormal cochlear hair cell development ( J:80025 )

• at E17.5, homozygotes display ectopic expression of the neuronal marker TUJ1 in outer hair cells, indicating abnormal OHC differentiation

decreased cochlear outer hair cell number ( J:80025 )

• at E16.5, homozygotes often have two OHC rows instead of the normal three

abnormal outer hair cell stereociliary bundle morphology ( J:80025 )

• at E18.5, mutant OHCs display abnormal or barely recognizable stereociliary bundles

abnormal cochlear OHC efferent innervation pattern ( J:80025 )

• remaining OHCs in the organ of Corti are not properly innervated

• in wild-type hair cells, cochlear neurons synapse with the base of the three OHCs forming a cup-like TUJ1 staining pattern at the base of eah OHC; in contrast, staining of mutant OHCs appears to be all over the cell body

cochlear hair cell degeneration ( J:80025 )

• by P14, all cochlear hair cells are lost by apoptosis

• in contrast, hair cells in the vestibular organs do not degenerate, but remain unorganized

• cochlear OHCs are the first to disappear starting at E17.5

• loss of hair cells occurs in a basal to apical gradient and affects OHCs prior to IHCs in any given region of the cochlea

cochlear inner hair cell degeneration ( J:80025 )

cochlear outer hair cell degeneration ( J:80025 )

• at E18.5, some OHCs display typical signs of apoptosis, i.e. shrinkage of the cell body, extensive blebbing and vacuolization; however, mutant OHC mitochondria appear normal

degeneration of organ of Corti supporting cells ( J:80025 )

• at P14, most supporting cells of the organ of Corti appear completely degenerated

organ of Corti degeneration ( J:80025 )

• at P14, the organ of Corti appears completely degenerated

abnormal vestibular hair cell morphology ( J:80025 )

• at E13.5, utricular hair cells are thinner and more elongated than wild-type cells

• at E14.5, vestibular hair cells fail to form a straight line at the edge of the lumen, and some are maintained in the support cell layer

• at P14, vestibular hair cells remain disorganized

• at 5 months, the saccule exhibits disorganized layering of hair and support cells

increased vestibular hair cell number ( J:80025 )

• at E14.5, vestibular hair cells display abnormal morphology and layering, with 2 to 3 layers instead of the single layer observed in wild-type epithelia

deafness ( J:80025 )

• by P14, homozygotes are presumably deaf, as they lack hair cells and a startle response to loud noises

nervous system

abnormal cochlear hair cell morphology ( J:80025 )

• at E18.5, homozygotes display disorganized hair cells in the organ of Corti

abnormal cochlear hair cell development ( J:80025 )

• at E17.5, homozygotes display ectopic expression of the neuronal marker TUJ1 in outer hair cells, indicating abnormal OHC differentiation

decreased cochlear outer hair cell number ( J:80025 )

• at E16.5, homozygotes often have two OHC rows instead of the normal three

abnormal outer hair cell stereociliary bundle morphology ( J:80025 )

• at E18.5, mutant OHCs display abnormal or barely recognizable stereociliary bundles

abnormal cochlear OHC efferent innervation pattern ( J:80025 )

• remaining OHCs in the organ of Corti are not properly innervated

• in wild-type hair cells, cochlear neurons synapse with the base of the three OHCs forming a cup-like TUJ1 staining pattern at the base of eah OHC; in contrast, staining of mutant OHCs appears to be all over the cell body

cochlear hair cell degeneration ( J:80025 )

• by P14, all cochlear hair cells are lost by apoptosis

• in contrast, hair cells in the vestibular organs do not degenerate, but remain unorganized

• cochlear OHCs are the first to disappear starting at E17.5

• loss of hair cells occurs in a basal to apical gradient and affects OHCs prior to IHCs in any given region of the cochlea

cochlear inner hair cell degeneration ( J:80025 )

cochlear outer hair cell degeneration ( J:80025 )

• at E18.5, some OHCs display typical signs of apoptosis, i.e. shrinkage of the cell body, extensive blebbing and vacuolization; however, mutant OHC mitochondria appear normal

abnormal vestibular hair cell morphology ( J:80025 )

• at E13.5, utricular hair cells are thinner and more elongated than wild-type cells

• at E14.5, vestibular hair cells fail to form a straight line at the edge of the lumen, and some are maintained in the support cell layer

• at P14, vestibular hair cells remain disorganized

• at 5 months, the saccule exhibits disorganized layering of hair and support cells

increased vestibular hair cell number ( J:80025 )

• at E14.5, vestibular hair cells display abnormal morphology and layering, with 2 to 3 layers instead of the single layer observed in wild-type epithelia

cochlear ganglion degeneration ( J:80025 )

• by 5 months of age, homozygotes show a dramatic loss of cochlear neurons through apoptosis

• cochlear ganglion neuron degeneration occurs at >P7 after hair cell loss and is progressive

Genotype
MGI:3696821

cx2

• Allelic Composition: Atoh1^tm2Hzo/Atoh1⁺; Gfi1^tm1Sho/Gfi1^tm1Sho
• Genetic Background: involves: 129S1/Sv * C57BL/6J

hearing/vestibular/ear

abnormal cochlear hair cell morphology ( J:80025 )

• at E15.5, the characteristic rows of IHCs and OHCs are not as clearly defined in the basal cochlea

• at E17.5, mutants display disorganization of hair cells and decreased hair cell numbers in the basal cochlea

• at P0, the apical cochlea shows little to no hair cell loss, but exhibits a disorganization similar to that seen in basal cochlea at E15.5

cochlear hair cell degeneration ( J:80025 )

• cochlear IHCs and OHCs are initially specified by E15.5 but are subsequently lost in a basal-to-apical gradient at P0

• by P3, the basal cochlea has few hair cells while the medial cochlea still retains most IHCs but has lost almost all OHCs

• in all cases, OHCs in a given region degenerate prior to IHCs cells

abnormal vestibular hair cell morphology ( J:80025 )

• at P0, the saccule shows disorganization of the hair cell layer, with some hair cells found in the supporting cell layer

• in contrast, cristae exhibit a relatively normal development of hair cells

abnormal vestibular hair cell stereociliary bundle morphology ( J:80025 )

• at P0, mutant vestibular hair cells appear to have less well organized stereocillia relative to wild-type hair cells

nervous system

abnormal cochlear hair cell morphology ( J:80025 )

• at E15.5, the characteristic rows of IHCs and OHCs are not as clearly defined in the basal cochlea

• at E17.5, mutants display disorganization of hair cells and decreased hair cell numbers in the basal cochlea

• at P0, the apical cochlea shows little to no hair cell loss, but exhibits a disorganization similar to that seen in basal cochlea at E15.5

cochlear hair cell degeneration ( J:80025 )

• cochlear IHCs and OHCs are initially specified by E15.5 but are subsequently lost in a basal-to-apical gradient at P0

• by P3, the basal cochlea has few hair cells while the medial cochlea still retains most IHCs but has lost almost all OHCs

• in all cases, OHCs in a given region degenerate prior to IHCs cells

abnormal vestibular hair cell morphology ( J:80025 )

• at P0, the saccule shows disorganization of the hair cell layer, with some hair cells found in the supporting cell layer

• in contrast, cristae exhibit a relatively normal development of hair cells

abnormal vestibular hair cell stereociliary bundle morphology ( J:80025 )

• at P0, mutant vestibular hair cells appear to have less well organized stereocillia relative to wild-type hair cells