Phenotypes associated with this allele

• Allele Symbol: Tg(BEST1-rtTA,tetO-cre)1Yzl
• Allele Name: transgene insertion 1, Yun-Zheng Le
• Allele ID: MGI:4398912
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Sod2^tm1Kskk/Sod2^tm1Kskk Tg(BEST1-rtTA,tetO-cre)1Yzl/0	B6.Cg-Sod2^tm1Kskk Tg(BEST1-rtTA,tetO-cre)1Yzl	MGI:6382792
cn2	Sod2^tm1Kskk/Sod2^tm1Kskk Tg(BEST1-rtTA,tetO-cre)1Yzl/0	B6J.Cg-Sod2^tm1Kskk Tg(BEST1-rtTA,tetO-cre)1Yzl	MGI:5774839
cn3	Dhdds^tm1.1Sjpi/Dhdds^tm1.1Sjpi Tg(BEST1-rtTA,tetO-cre)1Yzl/0	involves: C57BL/6J * FVB/N	MGI:6693811
cn4	Dhdds^tm1.1Sjpi/Dhdds^+ Tg(BEST1-rtTA,tetO-cre)1Yzl/0	involves: C57BL/6J * FVB/N	MGI:6693812

Genotype
MGI:6382792

cn1

• Allelic Composition: Sod2^tm1Kskk/Sod2^tm1Kskk; Tg(BEST1-rtTA,tetO-cre)1Yzl/0
• Genetic Background: B6.Cg-Sod2^tm1Kskk Tg(BEST1-rtTA,tetO-cre)1Yzl

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

vision/eye

retina pigment epithelium atrophy ( J:282248 )

• at age 6 and 9 months after doxycycline administration

thin retina outer nuclear layer ( J:282248 )

• at age 6 and 9 months after doxycycline administration

retina degeneration ( J:282248 )

• at age 6 and 9 months after doxycycline administration

decreased a-wave amplitude ( J:282248 )

• at age 6 and 9 months after doxycycline administration

decreased b-wave amplitude ( J:282248 )

• at age 6 and 9 months after doxycycline administration

pigmentation

retina pigment epithelium atrophy ( J:282248 )

• at age 6 and 9 months after doxycycline administration

Genotype
MGI:5774839

cn2

• Allelic Composition: Sod2^tm1Kskk/Sod2^tm1Kskk; Tg(BEST1-rtTA,tetO-cre)1Yzl/0
• Genetic Background: B6J.Cg-Sod2^tm1Kskk Tg(BEST1-rtTA,tetO-cre)1Yzl

vision/eye

abnormal ocular fundus morphology ( J:230153 )

• by 6 months of age, doxycycline-induced mice show discrete refractive foci in the fundus suggesting localized retinal degeneration

abnormal retina vasculature morphology ( J:230153 )

• doxycycline-induced mice show abnormal retinal blood vessels starting at ~6 months of age

• fluorescein angiography revealed vascular leakage in regions of atrophy, with twisted major blood vessels, vascular beading, and increased branching and dilation of deeper blood vessels

• however, no signs of choroidal neovascularization are observed

retina hemorrhage ( J:230153 )

• at 9 months of age, one doxycycline-induced mouse showed subretinal hemorrhage between the photoreceptors and RPE

abnormal retina pigment epithelium morphology ( J:230153 )

• at 6 weeks of age, neonatally doxycycline-induced mice show extensive oxidative damage to DNA in the RPE, as shown by 8-OHdG staining; most immunoreactivity is in the cytoplasm although some oxidative damage is seen in nuclei

• increased oxidative stress results in accumulation of 4-HNE-modified proteins and superoxide in the RPE

• at 4 months of age, autofluorescence in the RPE is increased by >20-fold, and basal infoldings of the RPE appear disordered

• by 9 months, overall RPE thickness is increased by ~30% relative to that at 1 month of age, with most thickening detected in the superior region (>40%)

abnormal retina pigmentation ( J:230153 )

• by 6 months, doxycycline-induced mice show hypopigmented areas and white spots reflected thinning of the retina

retina pigment epithelium atrophy ( J:230153 )

• doxycycline-induced mice show slowly progressive retina atrophy during aging

• at 6 months or later, large regions of the RPE appear to be absent, with no intact ONL or photoreceptor layer

• by 9 months, disc membranes are more widely spaced, fragmented mitochondria accumulate along the basal surface of the RPE, membrane-filled vacuoles are seen in some areas, and apical microvilli are absent

thin retina outer nuclear layer ( J:230153 )

• in doxycycline-induced mice, the average ONL thickness in the posterior retina is reduced by 15% by 6 months and by 24% by 9 months

abnormal retina photoreceptor layer morphology ( J:230153 )

• at 6 weeks of age, neonatally doxycycline-induced mice show increased accumulation of superoxide in the photoreceptor layer

short photoreceptor inner segment ( J:230153 )

• by 9 months, photoreceptor inner segments are severely shortened in some regions

short photoreceptor outer segment ( J:230153 )

• by 9 months, photoreceptor outer segments are severely shortened in some regions

abnormal retina rod cell outer segment morphology ( J:230153 )

• by 9 months, the length of rod outer segments is increased in many areas of the retina, with gaps between disc membranes

retina photoreceptor degeneration ( J:230153 )

abnormal optic choroid morphology ( J:230153 )

• at 4 months of age, neonatally doxycycline-induced mice show increased autofluorescence in the choroid

• at 6 months of age, the choroid layer shows distension and increased porosity

• by 9 months, the choroid appears less compact and more porous

abnormal Bruch membrane morphology ( J:230153 )

• at 4 months of age, doxycycline-induced mice show enlargement and disorganization of Bruch's membrane

abnormal cone electrophysiology ( J:230153 )

• doxycycline-induced mice show an age-related decline in the photopic b-wave amplitudes which becomes significant by 6 months

abnormal rod electrophysiology ( J:230153 )

• doxycycline-induced mice show an age-related decline in the scotopic a-wave and b-wave amplitudes which becomes significant by 6 months

cellular

oxidative stress ( J:230153 )

• at 2 months but not at 1 month of age, mice treated with doxycycline as pups show an 18% increase in nitrotyrosine in RPE/choroid samples, indicating increased oxidative stress

• increased oxidative stress in the RPE is confirmed by 8-OHdG staining and accumulation of 4-HNE-modified proteins and superoxide

pigmentation

abnormal retina pigment epithelium morphology ( J:230153 )

• at 6 weeks of age, neonatally doxycycline-induced mice show extensive oxidative damage to DNA in the RPE, as shown by 8-OHdG staining; most immunoreactivity is in the cytoplasm although some oxidative damage is seen in nuclei

• increased oxidative stress results in accumulation of 4-HNE-modified proteins and superoxide in the RPE

• at 4 months of age, autofluorescence in the RPE is increased by >20-fold, and basal infoldings of the RPE appear disordered

• by 9 months, overall RPE thickness is increased by ~30% relative to that at 1 month of age, with most thickening detected in the superior region (>40%)

abnormal retina pigmentation ( J:230153 )

• by 6 months, doxycycline-induced mice show hypopigmented areas and white spots reflected thinning of the retina

retina pigment epithelium atrophy ( J:230153 )

• doxycycline-induced mice show slowly progressive retina atrophy during aging

• at 6 months or later, large regions of the RPE appear to be absent, with no intact ONL or photoreceptor layer

• by 9 months, disc membranes are more widely spaced, fragmented mitochondria accumulate along the basal surface of the RPE, membrane-filled vacuoles are seen in some areas, and apical microvilli are absent

nervous system

short photoreceptor inner segment ( J:230153 )

• by 9 months, photoreceptor inner segments are severely shortened in some regions

short photoreceptor outer segment ( J:230153 )

• by 9 months, photoreceptor outer segments are severely shortened in some regions

abnormal retina rod cell outer segment morphology ( J:230153 )

• by 9 months, the length of rod outer segments is increased in many areas of the retina, with gaps between disc membranes

retina photoreceptor degeneration ( J:230153 )

cardiovascular system

abnormal retina vasculature morphology ( J:230153 )

• doxycycline-induced mice show abnormal retinal blood vessels starting at ~6 months of age

• fluorescein angiography revealed vascular leakage in regions of atrophy, with twisted major blood vessels, vascular beading, and increased branching and dilation of deeper blood vessels

• however, no signs of choroidal neovascularization are observed

retina hemorrhage ( J:230153 )

• at 9 months of age, one doxycycline-induced mouse showed subretinal hemorrhage between the photoreceptors and RPE

Genotype
MGI:6693811

cn3

• Allelic Composition: Dhdds^tm1.1Sjpi/Dhdds^tm1.1Sjpi; Tg(BEST1-rtTA,tetO-cre)1Yzl/0
• Genetic Background: involves: C57BL/6J * FVB/N

vision/eye

abnormal retina morphology ( J:287362 )

• display altered hyperreflective indicative of pathological changes

• descent of the external limiting membrane towards Bruchs membrane is seen

increased retina vascular tortuosity ( J:287362 )

• at 6 and 8 months of age

retina microaneurysm ( J:287362 )

• at 6 and 8 months of age

decreased retina photoreceptor cell number ( J:287362 )

• near total loss of photoreceptors in severely affected regions

abnormal photoreceptor outer segment morphology ( J:287362 )

• shortened, misshapen outer segments are seen throughout the retina

abnormal retina pigment epithelium morphology ( J:287362 )

• transmigration of RPE nuclei and melanosomes into the photoreceptor region (subretinal space and photoreceptor outer segment layer, and even deeper, into the ONL)

retina pigment epithelium atrophy ( J:287362 )

• display a geographic atrophy like retinal pigment epithelium (RPE) with the most degeneration observed mid-centrally throughout the retina

• areas of relatively intact tissue are seen in the periphery

• near total loss of RPE in severely affected regions

thin retina outer nuclear layer ( J:287362 )

• at 1, 2, and 3 months of age

decreased total retina thickness ( J:287362 )

• at 1, 2, and 3 months of age, particularly in the outer layer

decreased b-wave amplitude ( J:287362 )

• b-wave but not a-wave amplitudes are reduced

abnormal cone electrophysiology ( J:287362 )

• photopic responses are significantly lower at 1 month of age

abnormal rod electrophysiology ( J:287362 )

• reduced scotopic a-wave responses at 1 month of age

behavior/neurological

abnormal optokinetic reflex ( J:287362 )

• decrease in photopic and scotopic contrast sensitivity over the range of 0.031 to 0.272 c/d at 3 months of age

• however, no difference in spatial frequency is seen

cardiovascular system

increased retina vascular tortuosity ( J:287362 )

• at 6 and 8 months of age

retina microaneurysm ( J:287362 )

• at 6 and 8 months of age

nervous system

decreased retina photoreceptor cell number ( J:287362 )

• near total loss of photoreceptors in severely affected regions

abnormal photoreceptor outer segment morphology ( J:287362 )

• shortened, misshapen outer segments are seen throughout the retina

pigmentation

abnormal retina pigment epithelium morphology ( J:287362 )

• transmigration of RPE nuclei and melanosomes into the photoreceptor region (subretinal space and photoreceptor outer segment layer, and even deeper, into the ONL)

retina pigment epithelium atrophy ( J:287362 )

• display a geographic atrophy like retinal pigment epithelium (RPE) with the most degeneration observed mid-centrally throughout the retina

• areas of relatively intact tissue are seen in the periphery

• near total loss of RPE in severely affected regions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinitis pigmentosa 59		DOID:0110352	OMIM:613861	J:287362

Genotype
MGI:6693812

cn4

• Allelic Composition: Dhdds^tm1.1Sjpi/Dhdds⁺; Tg(BEST1-rtTA,tetO-cre)1Yzl/0
• Genetic Background: involves: C57BL/6J * FVB/N

vision/eye

decreased a-wave amplitude ( J:287362 )

• reduced at 3 months of age but not at 2 months

abnormal cone electrophysiology ( J:287362 )

• photopic b-wave responses are reduced at 2 and 3 months of age