Phenotypes Associated with This Genotype

Genotype
MGI:5637298

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

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

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