Phenotypes associated with this allele

• Allele Symbol: Pou4f2^tm1Nat
• Allele Name: targeted mutation 1, Jeremy Nathans
• Allele ID: MGI:2176272
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pou4f2^tm1Nat/Pou4f2^tm1Nat	B6.129S7-Pou4f2^tm1Nat	MGI:3842518
hm2	Pou4f2^tm1Nat/Pou4f2^tm1Nat	involves: 129S7/SvEvBrd * C57BL/6	MGI:3842433
cn3	Pou4f2^tm1Nat/Pou4f2^tm2.1Nat Tg(Pax6-cre,GFP)2Pgr/?	involves: 129S7/SvEvBrd	MGI:3842430
cx4	Atoh7^tm1Gan/Atoh7^tm1Gan Pou4f2^tm1Nat/Pou4f2^tm1Nat	B6.Cg-Pou4f2^tm1Nat Atoh7^tm1Gan	MGI:3842519

Genotype
MGI:3842518

hm1

• Allelic Composition: Pou4f2^tm1Nat/Pou4f2^tm1Nat
• Genetic Background: B6.129S7-Pou4f2^tm1Nat

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

vision/eye

decreased retina ganglion cell number ( J:135827 )

• retinal ganglion cells are decreased by about 80%

abnormal eye electrophysiology ( J:135827 )

• the saturated light-adapted b-wave is reduced in these mice

• ganglion function as measured by a small positive scotopic threshold response (STR) is absent in these mice

• the negative STR has a slightly faster time course than in controls

nervous system

decreased retina ganglion cell number ( J:135827 )

• retinal ganglion cells are decreased by about 80%

Genotype
MGI:3842433

hm2

• Allelic Composition: Pou4f2^tm1Nat/Pou4f2^tm1Nat
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

nervous system

decreased retina ganglion cell number ( J:32903 )

• retinal ganglion cell numbers are reduced by 70%

• large decreases in ganglion cell numbers occur as early as E13.5 suggesting a defect lies in precursor cells that give rise to retinal ganglion cells

optic nerve hypoplasia ( J:32903 )

• the diameter of the optic nerve is reduced 5-fold with a 1.5 fold drop in the density of axons present in the optic nerve

abnormal neuron physiology ( J:109300 )

• cultured dorsal root ganglion cells are completely resistant to death induced by withdrawal of nerve growth factor (NGF)

• sensory neurons from trigeminal or nodose ganglia are also resistant to death induced by the absence of neurotrophin or treatment with camptothecin

• virtually no losses of neurons occurs in vivo 7 and 11 days after sciatic nerve compared to considerable loss for in controls

• a 20% loss of neurons occurs 32 days after sciatic cell lesion compared to 70% in controls

vision/eye

impaired pupillary reflex ( J:147350 )

• the pupillary response to changes in ambient light level is greatly reduced in sensitivity and typically delayed by tens of seconds with wide variability

abnormal visual pursuit ( J:147350 )

• the optokinetic reflex to horizontal moving stimuli is reduced by about one-third and is completely abolished for vertical moving stimuli

decreased retina ganglion cell number ( J:32903 )

• retinal ganglion cell numbers are reduced by 70%

• large decreases in ganglion cell numbers occur as early as E13.5 suggesting a defect lies in precursor cells that give rise to retinal ganglion cells

optic nerve hypoplasia ( J:32903 )

• the diameter of the optic nerve is reduced 5-fold with a 1.5 fold drop in the density of axons present in the optic nerve

thin retina ganglion layer ( J:32903 )

• the number of nuclei in the ganglion cell layer is 30% less than in controls

thin retina inner nuclear layer ( J:32903 )

• the number of nuclei in the inner nuclear layer is 15% less than in controls

thin retina outer nuclear layer ( J:32903 )

• the number of nuclei in the outer nuclear layer is 10% less than in controls

retina hypoplasia ( J:32903 )

• the retina is 20% thinner than controls due to a decrease in the thickness of the inner plexiform, ganglion cell, and nerve fiber layers

• the number of nuclei in each of the retinal layers shows reductions of 30%, 15%, and 10% in the ganglion cell layer, the inner nuclear layer, and the outer nuclear layer, respectively

behavior/neurological

impaired pupillary reflex ( J:147350 )

• the pupillary response to changes in ambient light level is greatly reduced in sensitivity and typically delayed by tens of seconds with wide variability

abnormal visual pursuit ( J:147350 )

• the optokinetic reflex to horizontal moving stimuli is reduced by about one-third and is completely abolished for vertical moving stimuli

shortened circadian behavior period ( J:147350 )

• some mice exhibit activity with a period shorter than 24 hours regardless off light conditions

abnormal circardian behavior entrainment ( J:147350 )

• mice fail to synchronize to 6 hour shifts in the light/dark cycle

• mice also fail to respond to strong light

• percentage of daily activity that occurred within the light phase was 4.72% in controls, versus 39.12% in mutant mice during a 3.5/3.5-hour light/dark cycle

Genotype
MGI:3842430

cn3

• Allelic Composition: Pou4f2^tm1Nat/Pou4f2^tm2.1Nat; Tg(Pax6-cre,GFP)2Pgr/?
• Genetic Background: involves: 129S7/SvEvBrd

vision/eye

abnormal retina ganglion cell morphology ( J:147350 )

• retinal ganglion cells (RGC) have larger surface area and thick arbors

• some RGC axons follow aberrant trajectories, bifurcate within the retina or give rise to dendrite-like branches that ramify within the inner plexiform data

• a small percentage of RGC lack axons

• RGC cell body is more likely to reside in the inner nuclear layer (INL) than in the ganglion cell layer (GCL)

• the ratio of INL:GCL cell bodies is 178:105 compared with 9:147 for controls

• these misplaced RGC display morphological characteristics of glycinergic amacrine cells

• projections from the RGC are deficient to the olivary pretectal nucleus, the pretectal area and adjacent nucleus of the optic tract

• projections to the lateral and medial terminal nuclei are eliminated and the accessory optic tract is missing

decreased retina ganglion cell number ( J:147350 )

• 70% of retinal ganglion cells are not present

nervous system

abnormal optic tract morphology ( J:147350 )

• large decrements in RGC projections occur to the nucleus adjacent to the optic tract compared to controls

• the accessory optic tract is missing

• numerous neurites emerge at P4 from the optic tract and penetrate nearby nontarget areas

abnormal superior colliculus morphology ( J:147350 )

• large decrements in RGC projections occur to this part of the brain compared to controls

abnormal lateral geniculate nucleus morphology ( J:147350 )

• large decrements in RGC projections occur to this part of the brain compared to controls

abnormal retina ganglion cell morphology ( J:147350 )

• retinal ganglion cells (RGC) have larger surface area and thick arbors

• some RGC axons follow aberrant trajectories, bifurcate within the retina or give rise to dendrite-like branches that ramify within the inner plexiform data

• a small percentage of RGC lack axons

• RGC cell body is more likely to reside in the inner nuclear layer (INL) than in the ganglion cell layer (GCL)

• the ratio of INL:GCL cell bodies is 178:105 compared with 9:147 for controls

• these misplaced RGC display morphological characteristics of glycinergic amacrine cells

• projections from the RGC are deficient to the olivary pretectal nucleus, the pretectal area and adjacent nucleus of the optic tract

• projections to the lateral and medial terminal nuclei are eliminated and the accessory optic tract is missing

decreased retina ganglion cell number ( J:147350 )

• 70% of retinal ganglion cells are not present

Genotype
MGI:3842519

cx4

• Allelic Composition: Atoh7^tm1Gan/Atoh7^tm1Gan; Pou4f2^tm1Nat/Pou4f2^tm1Nat
• Genetic Background: B6.Cg-Pou4f2^tm1Nat Atoh7^tm1Gan

vision/eye

increased retina apoptosis ( J:135827 )

• at E16.5, there is a 65% increase in the number of apoptotic cells compared to controls

• at day of birth, apoptotic numbers are 500% greater than in controls

abnormal retina morphology ( J:135827 )

• a higher number of retinal cells are actively proliferating at E16.5

abnormal Muller cell morphology ( J:135827 )

• Muller cells are reduced by about 30%

decreased amacrine cell number ( J:135827 )

• there is a 70% reduction of amacrine cells

abnormal retina rod bipolar cell morphology ( J:135827 )

• rod bipolar cells are reduced by 45% and are found in patches instead of being evenly distributed

abnormal retina ganglion cell morphology ( J:135827 )

• the small number of retinal ganglion cells have small and underdeveloped axons

decreased retina ganglion cell number ( J:135827 )

• retinal ganglion cells are virtually absent with less than 1% of the normal number present

• cells are absent at birth suggesting an early developmental defect

thin retina ganglion layer ( J:135827 )

• the virtual absent of retinal ganglion cells leads to a decrease in layer thickness

thin retina inner nuclear layer ( J:135827 )

• there is a 65% reduction in the number of cells found in the inner nuclear layer including a 70% reduction of amacrine cells

thin retina outer nuclear layer ( J:135827 )

• there is a 50% reduction in the number of cells found in the outer nuclear layer

retina hypoplasia ( J:135827 )

• retinal thickness at the day of birth is reduced by about 50% compared to controls

abnormal eye electrophysiology ( J:135827 )

• b waves are significantly reduced under scotopic conditions and are absent under photopic conditions

nervous system

abnormal Muller cell morphology ( J:135827 )

• Muller cells are reduced by about 30%

decreased amacrine cell number ( J:135827 )

• there is a 70% reduction of amacrine cells

abnormal retina rod bipolar cell morphology ( J:135827 )

• rod bipolar cells are reduced by 45% and are found in patches instead of being evenly distributed

abnormal retina ganglion cell morphology ( J:135827 )

• the small number of retinal ganglion cells have small and underdeveloped axons

decreased retina ganglion cell number ( J:135827 )

• retinal ganglion cells are virtually absent with less than 1% of the normal number present

• cells are absent at birth suggesting an early developmental defect

cellular

increased retina apoptosis ( J:135827 )

• at E16.5, there is a 65% increase in the number of apoptotic cells compared to controls

• at day of birth, apoptotic numbers are 500% greater than in controls