Phenotypes Associated with This Genotype

Genotype
MGI:5609024

• Allelic Composition: Fam161a^{Gt(462E7)Cmhd}/Fam161a^{Gt(462E7)Cmhd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
• Cell Lines: 462E7

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

vision/eye

increased retina apoptosis ( J:214319 )

• increase in cell death in the retina beginning from 4 weeks of age and peaking at 5 months of age

abnormal retina photoreceptor morphology ( J:214319 )

• retinas lack clear photoreceptor inner/outer segment junctions

• photoreceptor cells show shortened connecting cilium, spread ciliary microtubule doublets and disturbed membrane disk organization

• however the structural arrangement of the basal body and the adjacent centriole of the cilium are not altered

abnormal photoreceptor connecting cilium morphology ( J:214319 )

• photoreceptor cells show shortened connecting cilium and spread ciliary microtubule doublets

• alternations in ciliary structures are seen in 95% of all photoreceptors as early as 4 weeks of age and by 10 weeks of age, all photoreceptor cells show defective cilia

abnormal photoreceptor outer segment morphology ( J:214319 )

• the outer segment base is dilated due to the spread ciliary microtubule doublets

• the membrane disk stacks in the outer segment are distorted, often arranged perpendicular to the disk stack orientation

• disk abnormalities are present in 60% of outer segments as early as 4 weeks of age and by 10 weeks of age, almost all photoreceptor outer segments are altered

disorganized photoreceptor outer segment ( J:214319 )

• retinas show disorganized photoreceptor outer segments already at 1 month of age

retina photoreceptor degeneration ( J:214319 )

• the elevated b/a-wave amplitude ratio indicates a photoreceptor-dominated degeneration

thin retina outer nuclear layer ( J:214319 )

• thinner outer nuclear layer is seen at 1 month of age

• more than 90% of the outer nuclear layer is lost after 6 months

retina outer nuclear layer degeneration ( J:214319 )

• gradual loss of the outer nuclear layer which is almost absent at 5 months of age

increased susceptibility to age-related retinal degeneration ( J:214319 )

• mice develop severe and progressive degeneration of the outer retina, involving a gradual loss of the outer nuclear layer which is almost absent at 5 months of age

• thinning of the outer retina is accompanied by disturbance of the structural order and the appearance of pyknotic photoreceptor nuclei and in later stages, the outer retina completely disappears, whereas the inner retina remains unaffected

abnormal electroretinogram waveform feature ( J:214319 )

• mice exhibit abnormal scotopic ERG responses already at 1 month of age and by 4 months, ERG responses are almost undetectable

increased a-wave implicit time ( J:214319 )

• at 1 month of age, the dark-adapted ERG response waveforms show prolonged implicit times for all flash intensities

increased b-wave implicit time ( J:214319 )

• at 1 month of age, the dark-adapted ERG response waveforms show prolonged implicit times for all flash intensities

decreased a-wave amplitude ( J:214319 )

• at 1 month of age, the dark-adapted ERG response waveforms show lower a- and b-wave amplitudes

• the light-adapted ERGs show a smaller effect than dark-adapted ERGs

decreased b-wave amplitude ( J:214319 )

• at 1 month of age, the dark-adapted ERG response waveforms show lower a- and b-wave amplitudes

• the light-adapted ERGs show a smaller effect than dark-adapted ERGs

abnormal vision ( J:214319 )

• early loss of visual function

cellular

abnormal photoreceptor connecting cilium morphology ( J:214319 )

• photoreceptor cells show shortened connecting cilium and spread ciliary microtubule doublets

• alternations in ciliary structures are seen in 95% of all photoreceptors as early as 4 weeks of age and by 10 weeks of age, all photoreceptor cells show defective cilia

increased retina apoptosis ( J:214319 )

• increase in cell death in the retina beginning from 4 weeks of age and peaking at 5 months of age

hematopoietic system

microgliosis ( J:214319 )

• reactive microglia increasingly accumulate in the subretinal space of older mice until the territorial microglial network is completely disrupted at 5 months of age

• microglia reactivity initiates at between 2 and 3 weeks of age, with maximum levels at 2 months

immune system

microgliosis ( J:214319 )

• reactive microglia increasingly accumulate in the subretinal space of older mice until the territorial microglial network is completely disrupted at 5 months of age

• microglia reactivity initiates at between 2 and 3 weeks of age, with maximum levels at 2 months

nervous system

microgliosis ( J:214319 )

• reactive microglia increasingly accumulate in the subretinal space of older mice until the territorial microglial network is completely disrupted at 5 months of age

• microglia reactivity initiates at between 2 and 3 weeks of age, with maximum levels at 2 months

abnormal retina photoreceptor morphology ( J:214319 )

• retinas lack clear photoreceptor inner/outer segment junctions

• photoreceptor cells show shortened connecting cilium, spread ciliary microtubule doublets and disturbed membrane disk organization

• however the structural arrangement of the basal body and the adjacent centriole of the cilium are not altered

abnormal photoreceptor connecting cilium morphology ( J:214319 )

• photoreceptor cells show shortened connecting cilium and spread ciliary microtubule doublets

• alternations in ciliary structures are seen in 95% of all photoreceptors as early as 4 weeks of age and by 10 weeks of age, all photoreceptor cells show defective cilia

abnormal photoreceptor outer segment morphology ( J:214319 )

• the outer segment base is dilated due to the spread ciliary microtubule doublets

• the membrane disk stacks in the outer segment are distorted, often arranged perpendicular to the disk stack orientation

• disk abnormalities are present in 60% of outer segments as early as 4 weeks of age and by 10 weeks of age, almost all photoreceptor outer segments are altered

disorganized photoreceptor outer segment ( J:214319 )

• retinas show disorganized photoreceptor outer segments already at 1 month of age

retina photoreceptor degeneration ( J:214319 )

• the elevated b/a-wave amplitude ratio indicates a photoreceptor-dominated degeneration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinitis pigmentosa 28		DOID:0110365	OMIM:606068	J:214319