Race: (BALB/c x Tyr^c) x lacZ-transgene

Inheritance: ar

Assignment: 7/X

Gene: Tyr

• melanine producing cells at:
  • choroid
  • optic stalk
  • RPE
• Choroidal melanine bearing cells develop after the optic chiasm has developed

• No relationship between:
  • pigment levels in choroid and the axon decussation pattern
  • axon position in the optic stalk relative to the pigmented cellsand the growth of the axon at the optic chiasma

• Crossed and uncrossed RGC express lacZ transgene at equal amounts
  => albino-mutation affects cell routing in an cell-extrensic manner
• Albino mutation acts indirectly on RGC

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Race:

Inheritance: ad

Assignment: 6

Gene: Rho

• Progressive shortening of ROS never being of normal age-match size
• Age-related decline of responses was paralleled by loss of rho density
• OS are formed at equivalent times
• OS are 50% of WT lengths
• Pyknotic nuclei

• Slow progressive degeneration of rods and cones

• Reduction in rod mediated response at 1 month
• Normal cone-mediated ERGs up to 5 months
• Rods do not recover after pre-bleach within 2 h
• Cone dysfunction subsequent to rod degeneration
• Results fit to equivalent light hypothesis

• No differences in chromophore binding and photic sensitivity
• Rho is translated and incorporated as usual
• Mutant and WT Rho seem to be present in ROS
• IR shows normal pattern and enhanced activity with anti-VPP Ab

• Abnormalities in dics membrane organization and synthesis

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Race:

Inheritance: ad

Assignment: 6

Gene: Rho

• Severe retinopathy
• Nearly complete at P30
• No elaboration of disc membrane or OS formation at any point

• More severe than knock-out phenotype alone

• Scotopic ERG a-wave is not produced

• Mutated Rho formed homodimers
• Expression level of mutated Rho was low (10 - 25%)
• Mutant protein localized to oerinuclear positions
• Reduced protein half life
• Inherent cytotoxicity of mutant protein attributable to UPR

• Compare to protein behavior of ninaE^D1 mutatnt in Drosophila

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Race:

Inheritance: ad

Assignment: 6 distal

Gene: Rho

Reduced decline of a-wave and b-wave amplitudes

• Vit A supplement of 2.5 and 102.5 mg as palmitate per kg of diet

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Race:

Inheritance: ad

Assignment: 6 distal

Gene: Rho

No effect on decline of amplitudes

• Vit A supplement of 2.5 and 102.5 mg as palmitate per kg of diet

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Race:

Inheritance: ar

Assignment: 19 proximal

Gene: rom1

• Photoreceptors die by apoptosis
• Death rate greater in young mice during first 6 months
• By 18 months 40% of photoreceptors have died
• Disorders OS after 1 month

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Inheritance: digenic

Assignment: 17/19

Gene: rds/rom1

• No retinal degeneration of (rds L185P) on (rds +/+, rom1 +/-) or (rds+/-. rom1+/+) background
• Slow progressive degeneration and significant OS dysplasia of (rds185P) on rom1-/- background

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Assignment: 17

Gene: rds

• Mildly dysplastic POS

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Inheritance: ar

Assignment:

Gene: Cln3

• Progressive storage of autofluorescent lipopigments
• Full fertility

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Gene: dlx-2

• Abnormal development of the forebrain
• Morphogenesis of the skeletal elements from first and second visceral arches was disturbed
• Homeobox expression pattern correlated with dlx-2 was not disturbed

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Inheritance: ar

Assignment:

Gene: emx

• Lack of discrete parts of the forebrain

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Gene: Gcap1/2

• a-waves increases on Gcap1 expresssion
• Majority of rods generated flash responses indistinguishable from WT
• Gcap2 does not restore the normal kinetics

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Gene: GC-E

• Loss of cone cells

• Substantial reduction of cone ERG
• ERG of knockout different from LCA patients

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Gene: Gnat1

• No morphological changes

• Homozygous cells do not produce a response
• No clear indication of responding cells by coulour tests

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Gene: IRBP

• Short OS
• Since P11
  • Loss of photoreceptor nuclei
  • Structural integrity of POS
• Slow progressive degeneration

• Reduced ERGs
• Marked loss in photic sensitivity by P30

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Race:

Inheritance: xl

Assignment: X

Gene: Ndg

• Increased number of blood vessels in the interface of GCL and NFL
• Decrease in IPL and OPL after P9
• Fenestrated vessels occasionally penetrate the ILM
• Disorganization and loss of cells in the GCL

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Inheritance: xl

Assignment: X

Gene: Ndg

• Severely atrophy spinal ganglion cells
• Atrophy and loss of ganglion cells in the cochlea primarily in the basal turn

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Race:

Inheritance: xl

Assignment: X

Gene: Ndg

• Fundus morphology equals wildtype in carrier
• Snowflake like vitreal changes in hemizygous
• Retinoschisis
• RPE irregularities in hemi and homozygotes
• Vitreous showed fibrouzs tissue at slit lamp examination
• Predominantly in GCL

• ERG normal in carriers
• In hemizygous severe loss of ERG b-wave
• negatively shaped scotopic ERG
• a-wave normal at low intensities
• Moderate amplitude loss at brighter flashes

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Race:

Inheritance: ar

Assignment:

Gene: Otx1

• -/-:
  • reduction of cerebral cortex
  • absence of sulcus rhinalis
  • shrunken hippocampus
  • enlarged inferior & superior colliculi of mesencephalon
  • absence of lacrimal and harderian gland
  • transient dwarfism and hypogonadism

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Race:

Inheritance: ar

Assignment:

Gene: Otx2

• -/-:
  • lethal
  • embryos die early during embryogenesis
  • lack of anterior neuroectoderm
  • major abnormalities in the body plan
  • headless phenotype

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Gene: Prkcg

• Mild deficits in spatial and contextual learning

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Inheritance: ar

Assignment:

Gene: Rgr

• Development of -/- appears normal
• No apparemt degeneration up to 9 months under cyclic house lighting

• Constant illumination at 900 lux for 4h
• -/- stimulkus response histogram is significant lower
• Scotopic ERG response consistent with lower rod sensitivity
• No difference in baseline ERG after dark adaptation

• RGR amount in +/- equals +/+ and is absent in -/-
• ~96% of RAl is 11cRAl in dark-adapted
• After 4000 lux /8h significant lower amonuts of 11cRAl in -/- with reduced amount of 11cRAl
• atRAl does not accumulate atRy overaccumulates in -/-

• Data obtained on free moving mice

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Gene: Rho

• Loss of OS in homozygous animal
• Disk moprphology is disturbed
• Reduced size of pineal
• Cone degeneration starting at P6w completein at P13w
• No abnormalitie sin RPE and choroid

• Plateau of ERG parameters between P4w and P6w with normal or subnormal cone responses and complete absence of rod contribution
• No ERG responses at P13w

• Model for pure cone function
• Developmental phase auntil P3w
• Marked onset of degeneration at P7w

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Gene: RmP

• 4.0 kb deletion results in no abnormal histology

• Dark adaptation is normal

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Race:

Inheritance: ar

Assignment: distal 3

Gene: Rpe65

• Histological differences to normal from 7th weeks of age on
• By 15 weeks thinning of OS layer
• RPE shows no major differences
• Overaccumulation of all-trans-retinyl esters in droplets
• +/+ and +/- mice share the same phenotype

• -/- shows diminished b-wave
• slow phot. Regeneration
• Heterozygotes show standard ERG
• In 9cRol fed mice: ERG shave larger amplitude and higher sensitivity
• Functional support for up to 6 month upon 9cRAl tretament

• Do not form 11cis-retinoids but Ry
• 1000fold higher Ry concentration compared to +/+ as cause of degeneration
• Isomerization step is affected in -/-
• No significant accumulation of 11cRol
• Oxidation of 11cRAl not affected

• Administration of 9cRol
• AP-1 is not activated in the absence of Rho
• Completely protected against light induced apoptosis
• atRAl is reduced and esterified
• 9cRAl recovers with time
• No adverse 9cRAl effects over time

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Race:

Inheritance: ar

Assignment:

Gene: Rpe65 / Cnga3

• Similiar ERGs were obtained from Rpe and Rpe/Cnga3 knockouts

• Model rules out cone involvement in Rpe65 deficient mice

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Race:

Inheritance: ar

Assignment:

Gene: Rpe65 / Rho

• Rho knockout ERGs do not match RPE65 knockout ERGs
• No response over the range of intensities tested

• Model supports rod involvement in Rpe65 deficient mice

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Inheritance: ar

Assignment:

Gene: Sag

• Photoreceptor loss:
  • Cyclic light: severe progressive after 100d (<50% survive after 1y)
  • Constant dark: indistinguishable form normals
  • Constant light: 30% loss after 1w and 60% after 3w

• Light induced damage suggests that patients with sag mutations are at higher risk of damaging effects by light

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Gene: Sag

• Cells are alive

• Very slow recovery of rod responses
• Cone responses are more or less normal

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Inheritance:

Assignment: 17

Gene: rds

• OS disorganization
• Photoreceptor degeneration
• Relatively preserved cones

• Decrease in Rmp3 of ERG by 3 weeks of age
• Further parameters stay unaffected

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Gene: Rbp

• RBP is synthesized from 7 d.p.c. on

• Markedly reduced retinal function through first months of life

• Reduced blood Rol levels
• With Vit A sufficient diet mice acquire normal visual function within 5 months
• Can acquire hepatic Rol stores that cannot be mobilized
• Vit A status depends on regular intake
• Normal ciculating RA levels

• Mice were viable and fertile
• TTR deficient mice have low circulating Rol levels
• Rbp acts due to the absent TTR-Rbp complex and not by the reduced serum Rol level

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Race:

Inheritance: ar

Assignment:

Gene: tulp1^-/-

• tulp1 is exclusively located in PIS
• Degeneration early involves rods and cones
• Opsins but not rds/peripherin show ectopic localization
• Massive accumulation of extracellular vesicles surrounding the distal IS

• Defect associated with loss of polarized transport of nascent opsins

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Inheritance: xl

Assignment: X

Gene: Xlrs1

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Race: B6C3xC3H; B6CBA/J; CSJL/J

Inheritance: ar

Assignment:

Gene: Pdeb

• rd/- mice produce
  • 1:1 mutant pre-mRNA: wt pre-mRNA
  • 1:3 mutant mRNA: wt mRNA
• Transcription of mutant and wt is similar but mutant transcript undergoes selective degredation during or after splicing

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Race: C57Bl/6

Inheritance:

Assignment:

Gene: Crbp1

• Normal anatomy

• Transient accumulation of atRAl and atRy after flash
• Rho not reduced
• atRy at 33% WT level
• CRBPI delivers atRol to LRAT
• Slower diffusion of atRAl

• Does not perturb the Ry production grossly
• Reduced hepatic Ry

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Race: C57BL/6

Inheritance: ad

Assignment:

Gene: Crx

• No POS
• No difference at P10
• At P14 and P21 OS were present only in +/- not in -/-
• Only thin ONL in -/- at P21
• Only shortend OS in +/- at P14
• +/- OS equal +/+ OS at P21

• No gross morphological abnormalities in -/- and +/- animals
• -/- and +/- are fertile and viable
• Circadian entrainment was affected

• Reduced expression of several photoreceptor- and pineal-specific genes

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Race: C57Bl/6

Inheritance:

Assignment:

Gene: Rlbp1

• Number of nuclei in ONL is higher than in WT albinos indicating a protective effect

• No evidence for photoreceptor degeneration in animals raised in light/dark cycle for 1y.

• Normal photosensivity
• Delayed dark adaptation
• Restoration of Rho after 80% bleach within 18-24h compared to ~1.5 h in WT and heterozygous knock-outs

• >10 fold delayed
  • Rho regeneration
  • 11cRAl production
• Accumulation of 11cRAl
• Rho not reduced

• Supports involvement of CRAlBP as an 11cRol acceptor in isomerisation

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Race: C57BL/6J

Inheritance: xl

Assignment: X

Gene: Oa1

• First pigment at E11-11.5
• Absence of giant melanosomes from E11.5-17.5
• Dispersion of giant and normal sized melanosomes throughout the pigment epithelium of iris, ciliary body, and retina at P1
• At P7 majority of melanosomes were giant

• No differences to normal mice over the full range of intensities
• Retinal function is not impaired in OA1
• Increased lable in the contralateral than ispilateral part of the visual pathway
• Crossing is favored in the optic chiasm

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Race: C57BL/6J

Inheritance:

Assignment:

Gene:

• First changes at P4-8
• In 3 w old mice most of the photoreceptors in the central retina have disappeared
• RPE enlarged with enlongated microvilli
• At 8 w complete loss of photoreceptors
• At 20 m 5-10% of choriocapillaris lost

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Race: C57BL/6J

Inheritance: ar

Assignment:

Gene: Tulp1

• Shortening of OS and IS by 2 w
• Greatly reduced thickness of ONL by 4 w
• ONL reduced to 1-2 rows at 12 w
• Loss of ONL by 20 w in some regions
• OS fragmented and distorted
• Fragmented IS with isolated PM bound vesicles

• Early onset retinal degeneration
• No obesity
• Rapid loss of photoreceptors
• Similar to P347S mice

• Reduced a- and b-wave from earliest time of testing (19 d) on
• Consistent with hypothesis: rod loss precedes cone loss
• Double heterozygotes (Tulp1/Tub) have normal ERG up to 6 m

• Ectopic accumulation of Rho at an early age
• Double knockouts (Tulp1/Tub) develop photorezeptors and express photorezeptor markers until 14d
• Thereafter fulminant degeneration
• Double heterozygotes are normal

• OPL collapsed by 6 m
• Vesicle accumulation is only transiently
• Not a failure of disc assembly or maintenance

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Race: C57BL/6x129v

Inheritance:

Assignment:

Gene: c-fos

• Lower mean ERG-amplitudes
• Marked variability
• Prolonged latencies
• 0.9 log unit lower b-wave
• Electron absorbance is not depending on c-fos

• Slightly reduced SAG levels
• 25% lower RHO level
• Phenotype rather results from missing c-fos in apoptotic cascade than deficits in rod function

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Race: C57Bl6J/SJL

Inheritance: ad

Assignment: 17

Gene: Mrg4

• Changes depend on age
• Extensive vacuolation of the outer plexiform layer
• Debris containing vacuoles
• Distorted synapses
• Swollen dendrites

• Age and transgene expression dependent phenotype
• Range from normal to white dots and streaks, to multiple flecks, to outright degeneration
• Lesion start at the superior temporal region

• Reduced b-wave
• c/b-wave ration is higher in the transgenics
• Result is consistent with abnormalities in the synaptic transmission from photoreceptors to secondary neurons

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Race: DBA/2J

Inheritance: ad

Assignment: 4

Gene:

• Reduction of retinal outer and plexiform layers at P10
• Loss after 6 weeks
• Retinal vessel attenuation
• pigment spots
• optic atrophy

• ERGs showed poorly after 3 - 6 weeks
• ERGs were barely detected after 6 weeks

• Excluded from RP1
• Encompasses nearly complete chromosome 4
• Homozygous lethal
• Locus near by or disrupted by breakpoint of inversion
• Breakpoints in 4A1 and 4E2 bands

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