Phenotypes associated with this allele

• Allele Symbol: Rdh8^tm1Kpal
• Allele Name: targeted mutation 1, Krzysztof Palczewski
• Allele ID: MGI:3586327
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rdh8^tm1Kpal/Rdh8^tm1Kpal	either: (involves: 129 * BALB/c) or (involves: 129 * C57BL/6J)	MGI:3605038
cx2	Abca4^tm1Kpal/Abca4^tm1Kpal Rdh8^tm1Kpal/Rdh8^tm1Kpal	involves: 129	MGI:6159294
cx3	Abca4^tm1Ght/Abca4^tm1Ght Rdh8^tm1Kpal/Rdh8^tm1Kpal	involves: 129 * 129S4/SvJae	MGI:4410294

Genotype
MGI:3605038

hm1

• Allelic Composition: Rdh8^tm1Kpal/Rdh8^tm1Kpal
• Genetic Background: either: (involves: 129 * BALB/c) or (involves: 129 * C57BL/6J)

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

vision/eye

delayed dark adaptation ( J:99930 )

• the rate at which all-trans-retinal is reduced to all-trans-retinol is slower

• following bleaching the recovery time of rods is significantly increased; however the initial extent of bleaching is similar to wild-type

Genotype
MGI:6159294

cx2

• Allelic Composition: Abca4^tm1Kpal/Abca4^tm1Kpal; Rdh8^tm1Kpal/Rdh8^tm1Kpal
• Genetic Background: involves: 129

vision/eye

abnormal eye morphology ( J:213619 )

• the eyecups of 6 month old mice contain the fluorescent by-product of retinal metabolism lipofusin pdA2E

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration		DOID:10871	OMIM:PS603075	J:213619
Stargardt disease		DOID:0050817	OMIM:248200 OMIM:600110 OMIM:603786	J:213619

Genotype
MGI:4410294

cx3

• Allelic Composition: Abca4^tm1Ght/Abca4^tm1Ght; Rdh8^tm1Kpal/Rdh8^tm1Kpal
• Genetic Background: involves: 129 * 129S4/SvJae

vision/eye

choroidal neovascularization ( J:154536 )

• choroidal neovascularization in 22.2% (2/9) of the eyes

• no choroidal neovascularization in the eyes of sirolimus-treated mice

abnormal retina photoreceptor morphology ( J:154536 )

decreased retina photoreceptor cell number ( J:154536 )

• reduced number of photoreceptor nuclei along the inferior retinal regions and severe retinal degeneration at 5 months and 10 months of age, respectively

decreased retina cone cell number ( J:154536 )

• reduced number of cone photoreceptors

• retinylamine treatment largely preserve cone photoreceptors

• antioxidant, 9cRAc, and sirolimus treatment preserve cone photoreceptors, but not as well as retinylamine

abnormal retina pigment epithelium morphology ( J:154536 )

• dead RPE cells lacking mitochondrial inner membrane cristae at 10 months of age

• swollen retinal pigment epithelium (RPE) with increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age

• disrupted inner membrane cristae in RPE cells at 5 months of age

abnormal retina pigmentation ( J:154536 )

• increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age

• di-retinoidpyridinium-ethanolamine (A2E) accumulation

• retinylamine significantly decreased A2E accumulation

thin retina outer nuclear layer ( J:154536 )

• severely reduced outer nuclear layer

retina degeneration ( J:154536 )

• early retinal degeneration is detected by 6 to 8 weeks of age in mice kept in dim room light (3-5 lux)

• reduced lengths of photoreceptor outer segments (less than 5 micrometers)

• antioxidant, 9cRAc, retinylamine and sirolimus treatment have efficacy in preventing retinal degeneration

retina deposits ( J:154536 )

• hyaline-like deposits in the rosette structure in 3- to 5-month-old mutant mice

abnormal Bruch membrane morphology ( J:154536 )

• complement deposition on Bruch's membrane

• reduced complement deposition in antioxidant, 9cRAc, and sirolimus-treated mice

• no complement deposition in retinylamine-treated mice

abnormal eye electrophysiology ( J:154536 )

abnormal cone electrophysiology ( J:154536 )

• reduced a- and b-wave amplitudes

• both a- and b-wave amplitudes are maintained significantly better in antioxidant, 9cRAc, retinylamine and sirolimus-treated mice

abnormal rod electrophysiology ( J:154536 )

• reduced Flicker ERG responses

• responses of some antioxidant- and 9cRAc-treated mice are significantly retained after both 20- and 30-Hz stimuli

nervous system

abnormal retina photoreceptor morphology ( J:154536 )

decreased retina photoreceptor cell number ( J:154536 )

• reduced number of photoreceptor nuclei along the inferior retinal regions and severe retinal degeneration at 5 months and 10 months of age, respectively

decreased retina cone cell number ( J:154536 )

• reduced number of cone photoreceptors

• retinylamine treatment largely preserve cone photoreceptors

• antioxidant, 9cRAc, and sirolimus treatment preserve cone photoreceptors, but not as well as retinylamine

pigmentation

abnormal retina pigment epithelium morphology ( J:154536 )

• swollen retinal pigment epithelium (RPE) with increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age

• disrupted inner membrane cristae in RPE cells at 5 months of age

• dead RPE cells lacking mitochondrial inner membrane cristae at 10 months of age

abnormal retina pigmentation ( J:154536 )

• increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age

• di-retinoidpyridinium-ethanolamine (A2E) accumulation

• retinylamine significantly decreased A2E accumulation

cardiovascular system

choroidal neovascularization ( J:154536 )

• choroidal neovascularization in 22.2% (2/9) of the eyes

• no choroidal neovascularization in the eyes of sirolimus-treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration 2		DOID:0110015	OMIM:153800	J:154536