Phenotypes associated with this allele

• Allele Symbol: Tg(BEST1-cre)1Jdun
• Allele Name: transgene insertion 1, Joshua L Dunaief
• Allele ID: MGI:4946605
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan Tg(BEST1-cre)1Jdun/0	involves: 129P2/OlaHsd * C57BL/6	MGI:6382980
cn2	Cryba1^tm1.1Dbsa/Cryba1^tm1.1Dbsa Tg(BEST1-cre)1Jdun/0	involves: 129S6/SvEvTac * C57BL/6	MGI:5637298
cn3	Spata7^tm1Mrd/Spata7^tm2Mrd Tg(BEST1-cre)1Jdun/0	involves: 129S7/SvEvBrd * C57BL/6	MGI:6386740
cn4	Cp^tm1Hrs/Cp^tm1Hrs Heph^tm1.1Jdun/Heph^tm1.1Jdun Tg(BEST1-cre)1Jdun/0 Tg(Rho-cre)#Yzl/0	involves: 129X1/SvJ * C57BL/6 * C57BL/6NTac	MGI:5490775
cn5	Cp^tm1Hrs/Cp^tm1Hrs Heph^tm1.1Jdun/Heph^tm1.1Jdun Tg(BEST1-cre)1Jdun/0	involves: 129X1/SvJ * C57BL/6 * C57BL/6NTac	MGI:5490772
cn6	Heph^tm1.1Jdun/Heph^tm1.1Jdun Tg(BEST1-cre)1Jdun/0	involves: C57BL/6 * C57BL/6NTac	MGI:5490769

Genotype
MGI:6382980

cn1

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan; Tg(BEST1-cre)1Jdun/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

vision/eye

vision/eye phenotype ( J:282249 )

N • normal retinal outer nuclear layer and total retina thickness at age 2 months

N • normal scotopic and photopic ERGs at age 2 months

N • normal retinal vasculature at age 4 months

N • normal levels of autophagy markers in photoreceptor layer

abnormal retina pigment epithelium morphology ( J:282249 )

• small, white-yellowish structures and patchy atrophy beginning at 4 months

• scattered foci of RPE hyperpigmentation

• invasion of macrophages at age 4 months

• vacuolization at age 8 months

• disorganized at age 8 months

• normal morphology at age 2 months

abnormal retina pigmentation ( J:282249 )

• patchy hyperpigmentation at boundaries with atrophic patches at age 4 months

• hyper-reflective foci above the RPE reflectance layer at age 4 months

retina pigment epithelium atrophy ( J:282249 )

• beginning at 4 months

thin retina outer nuclear layer ( J:282249 )

• at age 8 months

disorganized retina outer nuclear layer ( J:282249 )

• at age 8 months

abnormal retina photoreceptor layer morphology ( J:282249 )

• disorganized at age 8 months

disorganized retina layers ( J:282249 )

• at age 8 months

increased susceptibility to age-related retinal degeneration ( J:282249 )

• age-dependent degeneration secondary to reduced autophagy in retinal pigment epithelium

abnormal Bruch membrane morphology ( J:282249 )

• disrupted at age 8 months

• occasional ingrowth of blood vessels from choroid to outer retina

decreased b-wave amplitude ( J:282249 )

• progressive reduction between age 2 and 8 months with photopic and scotopic ERG

abnormal cone electrophysiology ( J:282249 )

• age-dependent reduction

abnormal rod electrophysiology ( J:282249 )

• age-dependent reduction

cellular

impaired autophagy ( J:282249 )

• in the retinal pigment epithelium

hematopoietic system

microgliosis ( J:282249 )

• in response to retinal degeneration

homeostasis/metabolism

impaired autophagy ( J:282249 )

• in the retinal pigment epithelium

immune system

microgliosis ( J:282249 )

• in response to retinal degeneration

nervous system

microgliosis ( J:282249 )

• in response to retinal degeneration

pigmentation

abnormal retina pigment epithelium morphology ( J:282249 )

• scattered foci of RPE hyperpigmentation

• invasion of macrophages at age 4 months

• vacuolization at age 8 months

• disorganized at age 8 months

• small, white-yellowish structures and patchy atrophy beginning at 4 months

• normal morphology at age 2 months

abnormal retina pigmentation ( J:282249 )

• patchy hyperpigmentation at boundaries with atrophic patches at age 4 months

• hyper-reflective foci above the RPE reflectance layer at age 4 months

retina pigment epithelium atrophy ( J:282249 )

• beginning at 4 months

lipofuscinosis ( J:282249 )

• accumulation of lipid-filled vacuoles and mitochondria in the retinal pigment epithelium

Genotype
MGI:5637298

cn2

• Allelic Composition: Cryba1^tm1.1Dbsa/Cryba1^tm1.1Dbsa; Tg(BEST1-cre)1Jdun/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

cellular

abnormal lysosome morphology ( J:215838 )

• decrease in type I lysosomes (a type of autophagic melano-lysosome)

impaired autophagy ( J:215838 )

• autophagy is decreased in the retinal pigment epithelium (RPE)

abnormal lysosome physiology ( J:215838 )

• lysosomal-mediated clearance is inhibited in the RPE

• autophagosomes accumulate in the RPE due to inhibition of the proteolytic degradation by the lysosomes

• endolysosomal pH is about 0.7 pH units higher in primary RPE cells than in wild-type cells

lysosomal protein accumulation ( J:215531 )

• lysosomal-mediated clearance is impaired in the retina

homeostasis/metabolism

impaired autophagy ( J:215838 )

• autophagy is decreased in the retinal pigment epithelium (RPE)

pigmentation

abnormal retina pigment epithelium morphology ( J:215531 , J:215838 )

• 12 month old mice show retinal pigment epithelium degeneration, including loss of basal infoldings, prominent intracellular vacuoles, undigested melanosomes and photoreceptor outer segments, widening of adherens junctions, and an increase in cell death in the RPE (J:215531)

• the tightly connected monolayer of pigment cells with cuboidal morphology, well-defined cell junctions, apical microvilli, and basal infoldings is disrupted in aging mice (J:215838)

• abnormal lipid accumulation in the retinal pigment epithelium (J:215838)

• vacuole-like structures, some with undigested outer segments, and loss and truncation of basal infoldings, are seen in the RPE as early as 2 months of age (J:215838)

• by 9 months of age, large vacuoles containing partially degradative autophagic vacuoles are seen (J:215838)

abnormal retina pigmentation ( J:215838 )

• the retinal pigment epithelium shows areas of hypo- and hyper-pigmentation and scattered lesions by 4 months of age that increases with age

• increase in the number of melanosomes in the RPE

vision/eye

abnormal retina pigment epithelium morphology ( J:215531 , J:215838 )

• 12 month old mice show retinal pigment epithelium degeneration, including loss of basal infoldings, prominent intracellular vacuoles, undigested melanosomes and photoreceptor outer segments, widening of adherens junctions, and an increase in cell death in the RPE (J:215531)

• the tightly connected monolayer of pigment cells with cuboidal morphology, well-defined cell junctions, apical microvilli, and basal infoldings is disrupted in aging mice (J:215838)

• abnormal lipid accumulation in the retinal pigment epithelium (J:215838)

• vacuole-like structures, some with undigested outer segments, and loss and truncation of basal infoldings, are seen in the RPE as early as 2 months of age (J:215838)

• by 9 months of age, large vacuoles containing partially degradative autophagic vacuoles are seen (J:215838)

abnormal retina pigmentation ( J:215838 )

• the retinal pigment epithelium shows areas of hypo- and hyper-pigmentation and scattered lesions by 4 months of age that increases with age

• increase in the number of melanosomes in the RPE

increased susceptibility to age-related retinal degeneration ( J:215531 )

• mice slowly develop age-related macular degeneration-like pathology associated with inefficient lysosomal clearance

decreased a-wave amplitude ( J:215838 )

• at 7 months of age, mice show reductions in both scotopic a-wave and photopic b-wave amplitudes indicating both rod and cone photoreceptor dysfunction

decreased b-wave amplitude ( J:215838 )

• mice show a reduction in photopic b-wave amplitudes at the two highest stimulus intensities at 4 months of age, indicating cone photoreceptor dysfunction

• at 7 months of age, mice show reductions in both scotopic a-wave and photopic b-wave amplitudes indicating both rod and cone photoreceptor dysfunction

nervous system

gliosis ( J:215531 )

• GFAP-expressing activated Muller cells are present in the retina, indicating reactive gliosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration 1		DOID:0110014	OMIM:603075	J:215531

Genotype
MGI:6386740

cn3

• Allelic Composition: Spata7^tm1Mrd/Spata7^tm2Mrd; Tg(BEST1-cre)1Jdun/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

vision/eye

vision/eye phenotype ( J:279827 )

N • mice exhibit normal retinal morphology with no signs of photoreceptor degeneration

Genotype
MGI:5490775

cn4

• Allelic Composition: Cp^tm1Hrs/Cp^tm1Hrs; Heph^tm1.1Jdun/Heph^tm1.1Jdun; Tg(BEST1-cre)1Jdun/0; Tg(Rho-cre)#Yzl/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * C57BL/6NTac

homeostasis/metabolism

abnormal iron level ( J:196540 )

♀ • iron levels in retinal pigment epithelium cells are not increased beyond levels in Cp^tm1Hrs/Cp^tm1Hrs Heph^tm1.1Itl/ Heph^tm1.1Itl Tg(BEST1-cre)1Jdun mice

abnormal protein level ( J:196540 )

♀ • bipolar cells exhibit an increase in L-ferritin levels

Genotype
MGI:5490772

cn5

• Allelic Composition: Cp^tm1Hrs/Cp^tm1Hrs; Heph^tm1.1Jdun/Heph^tm1.1Jdun; Tg(BEST1-cre)1Jdun/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * C57BL/6NTac

vision/eye

abnormal retina pigment epithelium morphology ( J:196540 )

♀ • retinal pigment epithelium (RPE) cells exhibit atrophy, hypertrophy and large vacuoles with cells extruded into the photoreceptor layer

♀ • however, PRE cells are not auto-fluorescent

retina pigment epithelium atrophy ( J:196540 )

♀

homeostasis/metabolism

abnormal iron level ( J:196540 )

♀ • increased iron accumulation in the retinal pigment epithelium at 3 months of age

♀ • increased transferrin receptor levels are decreased in the retinal pigment epithelium and neural retinas indicating increased labile iron levels

pigmentation

abnormal retina pigment epithelium morphology ( J:196540 )

♀ • retinal pigment epithelium (RPE) cells exhibit atrophy, hypertrophy and large vacuoles with cells extruded into the photoreceptor layer

♀ • however, PRE cells are not auto-fluorescent

retina pigment epithelium atrophy ( J:196540 )

♀

Genotype
MGI:5490769

cn6

• Allelic Composition: Heph^tm1.1Jdun/Heph^tm1.1Jdun; Tg(BEST1-cre)1Jdun/0
• Genetic Background: involves: C57BL/6 * C57BL/6NTac

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:196540 )

♀N • mice exhibit normal circulating and retinal pigment epithelium iron levels