Phenotypes Associated with This Genotype

Genotype
MGI:5527432

• Allelic Composition: Ccl2^tm1Rol/Ccl2^tm1Rol; Cx3cr1^tm1Litt/Cx3cr1^tm1Litt
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J

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

Retinal lesion in Ccl2^tm1Rol/Ccl2^tm1Rol Cx3cr1^tm1Litt/Cx3cr1^tm1Litt mice

vision/eye

abnormal retina morphology ( J:200877 )

• patches of yellowish/whitish fundus lesions are seen in 17-60% of 12 month old and 30-100% of 18 month old mutants

• majority of lesions are in the temporal area (upper and lower) between the optic disc and equatorial region of the retina, with variable lesion size and lesions are rarely seen in the peripheral retinal areas

• 83-100% of mutants exposed to an approximate 800 lux light 6 hours/day for 6-7 months develop patches of yellowish and whitish lesions compared to 20-25% of wild-type mice

• aged and light-treated mutant retinas exhibit mitochondrial damage, vacuolization, and photoreceptor damage

• however, choroidal neovascularization is not seen in aged or 800 lux light treated mutants and induction of choroidal neovascularization using 532 nm diode laser does not differ from that seen in wild-type mice

abnormal Muller cell morphology ( J:200877 )

• increase in Muller glial activation

abnormal amacrine cell morphology ( J:200877 )

• expression of rhodopsin, cone arrestin, and GABA are disrupted suggesting amacrine cell changes in aged mutants

abnormal photoreceptor inner segment morphology ( J:200877 )

• photoreceptor inner segment damage in aged mutants

disorganized photoreceptor outer segment ( J:200877 )

• outer segment disorientation in aged mutants

retina photoreceptor degeneration ( J:200877 )

• expression of rhodopsin, cone arrestin, and GABA are disrupted suggesting photoreceptor degeneration

abnormal retina pigmentation ( J:200877 )

• older mutants exhibit pigment loss in RPE cells

retina pigment epithelium atrophy ( J:200877 )

• 33% of 12 month old and 50% of 18 month old mutants exhibit retinal pigment epithelium (RPE) damage, showing altered cell junction, loss of hexagonal tessellation, and uneven distribution of F-actin

• older mutants exhibit multiple vacuoles in the RPE

• all mutants exhibit RPE lesions after light-treatment (800 Lux) compared to 20% of wild-type mice

increased susceptibility to age-related retinal degeneration ( J:200877 )

• mice develop age- and light-mediated retinal damage

abnormal Bruch membrane morphology ( J:200877 )

• increase in Bruch membrane thickness in aged mutants

pigmentation

abnormal retina pigmentation ( J:200877 )

• older mutants exhibit pigment loss in RPE cells

retina pigment epithelium atrophy ( J:200877 )

• 33% of 12 month old and 50% of 18 month old mutants exhibit retinal pigment epithelium (RPE) damage, showing altered cell junction, loss of hexagonal tessellation, and uneven distribution of F-actin

• older mutants exhibit multiple vacuoles in the RPE

• all mutants exhibit RPE lesions after light-treatment (800 Lux) compared to 20% of wild-type mice

nervous system

abnormal microglial cell morphology ( J:200877 )

• microglial cells in aged and chronic light-treated mice show shorter and larger dendrites and larger somas

increased microglial cell activation ( J:200877 )

• increase in microglial activation as indicated by an increase in microglial cells in the inner plexiform layer and the outer plexiform layer at 18 months of age and in chronic-light treated mutants

abnormal Muller cell morphology ( J:200877 )

• increase in Muller glial activation

abnormal amacrine cell morphology ( J:200877 )

• expression of rhodopsin, cone arrestin, and GABA are disrupted suggesting amacrine cell changes in aged mutants

abnormal photoreceptor inner segment morphology ( J:200877 )

• photoreceptor inner segment damage in aged mutants

disorganized photoreceptor outer segment ( J:200877 )

• outer segment disorientation in aged mutants

retina photoreceptor degeneration ( J:200877 )

• expression of rhodopsin, cone arrestin, and GABA are disrupted suggesting photoreceptor degeneration

hematopoietic system

abnormal microglial cell morphology ( J:200877 )

• microglial cells in aged and chronic light-treated mice show shorter and larger dendrites and larger somas

abnormal macrophage physiology ( J:200877 )

• bone marrow derived macrophages exhibit reduced phagocytic activity

increased microglial cell activation ( J:200877 )

• increase in microglial activation as indicated by an increase in microglial cells in the inner plexiform layer and the outer plexiform layer at 18 months of age and in chronic-light treated mutants

immune system

abnormal microglial cell morphology ( J:200877 )

• microglial cells in aged and chronic light-treated mice show shorter and larger dendrites and larger somas

abnormal macrophage physiology ( J:200877 )

• bone marrow derived macrophages exhibit reduced phagocytic activity

increased microglial cell activation ( J:200877 )

• increase in microglial activation as indicated by an increase in microglial cells in the inner plexiform layer and the outer plexiform layer at 18 months of age and in chronic-light treated mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration		DOID:10871	OMIM:PS603075	J:200877