Phenotypes associated with this allele

• Allele Symbol: Abca4^tm1Ght
• Allele Name: targeted mutation 1, Gabriel H Travis
• Allele ID: MGI:1857860
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Abca4^tm1Ght/Abca4^tm1Ght	involves: 129S4/SvJae	MGI:3697458
hm2	Abca4^tm1Ght/Abca4^tm1Ght	involves: 129S4/SvJae * BALB/c	MGI:3820396
hm3	Abca4^tm1Ght/Abca4^tm1Ght	involves: 129S4/SvJae * C57BL/6	MGI:2653823
cx4	Abca4^tm1Ght/Abca4^tm1Ght Rdh8^tm1Kpal/Rdh8^tm1Kpal	involves: 129 * 129S4/SvJae	MGI:4410294

Genotype
MGI:3697458

hm1

• Allelic Composition: Abca4^tm1Ght/Abca4^tm1Ght
• Genetic Background: involves: 129S4/SvJae

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

vision/eye

abnormal retina pigment epithelium morphology ( J:141801 )

• levels of lipofuscin and its associated metabolites are 20-fold higher than in controls in the retinal pigment epithelium of mice supplemented with vitamin A

abnormal eye physiology ( J:117483 )

• A2E fluorescent product (from condensation of all-trans-retinal) is detected at much higher levels than in wild-type or Rdh12-deficient mice

homeostasis/metabolism

abnormal vitamin A level ( J:141801 )

• mice supplemented with vitamin A accumulate more higher levels of all-trans retinoic acid in both the liver and eyes

pigmentation

abnormal retina pigment epithelium morphology ( J:141801 )

• levels of lipofuscin and its associated metabolites are 20-fold higher than in controls in the retinal pigment epithelium of mice supplemented with vitamin A

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cone-rod dystrophy 3		DOID:0111013	OMIM:604116	J:141801
retinitis pigmentosa 19		DOID:0110354	OMIM:601718	J:141801
Stargardt disease		DOID:0050817	OMIM:248200 OMIM:600110 OMIM:603786	J:141801

Genotype
MGI:3820396

hm2

• Allelic Composition: Abca4^tm1Ght/Abca4^tm1Ght
• Genetic Background: involves: 129S4/SvJae * BALB/c

vision/eye

photoreceptor outer segment degeneration ( J:141801 )

• the outer segment is approximately 40% degenerated with OS shortening by 11 months of age

abnormal retina pigment epithelium morphology ( J:141801 )

• levels of lipofuscin and its associated metabolites are higher than in controls in the retinal pigment epithelium of mice, especially when diet is supplemented with vitamin A

• the fractional area of lipofuscin granules in the RPE is 0.11 and reaches 0.14 when supplemented with vitamin A as compared to 0.053 in albino controls fed a control diet

thin retina outer nuclear layer ( J:141801 )

• the outer nuclear layer of 11-month old albinos contains 6 to 7 rows compared to 10 to 11 rows for controls

pigmentation

abnormal retina pigment epithelium morphology ( J:141801 )

• levels of lipofuscin and its associated metabolites are higher than in controls in the retinal pigment epithelium of mice, especially when diet is supplemented with vitamin A

• the fractional area of lipofuscin granules in the RPE is 0.11 and reaches 0.14 when supplemented with vitamin A as compared to 0.053 in albino controls fed a control diet

nervous system

photoreceptor outer segment degeneration ( J:141801 )

• the outer segment is approximately 40% degenerated with OS shortening by 11 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cone-rod dystrophy 3		DOID:0111013	OMIM:604116	J:141801
retinitis pigmentosa 19		DOID:0110354	OMIM:601718	J:141801
Stargardt disease		DOID:0050817	OMIM:248200 OMIM:600110 OMIM:603786	J:141801

Genotype
MGI:2653823

hm3

• Allelic Composition: Abca4^tm1Ght/Abca4^tm1Ght
• Genetic Background: involves: 129S4/SvJae * C57BL/6

vision/eye

abnormal photoreceptor outer segment morphology ( J:56317 )

• mutants exhibit a 1.6-fold increase in phosphatidyletanolamine in the outer segments of retinal pigment epithelium

• mutants exhibit the presence of protonated and absence of nonprotonated N-retinylidene-phosphatidylethanolamine in outer segments

retina photoreceptor degeneration ( J:56317 )

• mutants show a 35% mean reduction in a-wave amplitude up to 1 year of age, suggesting a slow photoreceptor degeneration

abnormal retina pigment epithelium morphology ( J:56317 )

• 16 and 20 week old mutants exhibit lipofuscin accumulation in the retinal pigment epithelium

• 44 week old eyes show accumulation of dense bodies within retinal pigment epithelium cells, including large oval structures of high electron density

abnormal Bruch membrane morphology ( J:56317 )

• Bruch's membrane between the retinal pigment epithelium and choroid is thickened

abnormal eye physiology ( J:56317 )

• mutants exhibit a transient accumulation of all-trans- retinaldehyde and transient depletion of all-trans-retinol and all-trans-retinyl esters following photobleach

delayed dark adaptation ( J:56317 )

nervous system

abnormal photoreceptor outer segment morphology ( J:56317 )

• mutants exhibit a 1.6-fold increase in phosphatidyletanolamine in the outer segments of retinal pigment epithelium

• mutants exhibit the presence of protonated and absence of nonprotonated N-retinylidene-phosphatidylethanolamine in outer segments

retina photoreceptor degeneration ( J:56317 )

• mutants show a 35% mean reduction in a-wave amplitude up to 1 year of age, suggesting a slow photoreceptor degeneration

pigmentation

abnormal retina pigment epithelium morphology ( J:56317 )

• 16 and 20 week old mutants exhibit lipofuscin accumulation in the retinal pigment epithelium

• 44 week old eyes show accumulation of dense bodies within retinal pigment epithelium cells, including large oval structures of high electron density

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Stargardt disease		DOID:0050817	OMIM:248200 OMIM:600110 OMIM:603786	J:56317

Genotype
MGI:4410294

cx4

• 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 )

• 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

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