Phenotypes Associated with This Genotype

Genotype
MGI:3797222

• Allelic Composition: Vldlr^tm1Her/Vldlr^tm1Her
• Genetic Background: B6;129S7-Vldlr^tm1Her/J

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

vision/eye

choroidal neovascularization ( J:132497 )

• CNV membranes develop after 6 months of age with some tissue destruction in INL and ONL

• some retinal-choroidal anastomoses may be observed at 10 months

abnormal retina morphology ( J:128315 , J:132497 )

• accumulation of cell debris is observed prior to development of intraretinal neovascularization (J:128315)

• angiomatous growths are densely distributed throughout retina at 4 weeks (J:132497)

• at 6 weeks, scattered pink spots progress to large, irregular pink areas by 6 months; leaking spots decrease after 8 months with large rigid vascular tangles still present and leakage is barely detectable by 12 months (J:132497)

• fibrosis formation is present at 12 months, beginning around 3 months with fibroblast accumulation at lesion site (J:132497)

retina neovascularization ( J:128315 , J:132497 )

• new vessels form in outer plexiform layer of retina around 3 weeks of age; vessels migrate into subretinal space by 4 weeks (J:128315)

• angiography shows leakage in retinas at 6 weeks, mainly in central area of retina near optic nerve, with red blood cells found around the leakage spot; neovascularization is localized to outer nuclear layer and in subretinal space (J:128315)

• signs of new vessel growth is observed at 14 days in deep capillary bed of outer plexiform layer (OPL) of retina, protruding into avascular zone of outer nuclear layer (ONL) (J:132497)

• new vessel buds reach subretinal space by P15 (J:132497)

• leakage is first seen at 3 weeks and increases with age, with leaking areas covering most of retinal by 6 weeks (J:132497)

• clumps of retinal pigmented epithelial cells (RPE) adhere to neovascular tufts in subretinal space; these increase with age (J:132497)

• subretinal neovascularization (SRN) is seen at 6 weeks of age (J:132497)

• fibrosis formation is present at 12 months, beginning around 3 months with fibroblast accumulation at lesion site (J:132497)

abnormal retina pigment epithelium morphology ( J:128315 , J:132497 )

• thickening of RPE cells is observed prior to development of intraretinal neovascularization (J:128315)

• disruption of RPE layer is observed by 6 weeks of age (J:132497)

• pigment adhesions to neural tissue are seen by 6 weeks, representing pigment epithelium detachment (J:132497)

abnormal retina neuronal layer morphology ( J:128315 )

• between 6 and 8 weeks, both outer and inner segments are disrupted in lesion area; migration of RPE cells into lesion area is observed

decreased retina photoreceptor cell number ( J:128315 , J:132497 )

• significant loss of photoreceptors is seen at 6 months, resulting in thinning of outer nuclear layer (J:128315)

• increased loss is detected at 12 months (J:132497)

retina photoreceptor degeneration ( J:132497 )

• observed at 10 months

disorganized retina inner nuclear layer ( J:128315 )

• by 4 weeks

thin retina outer nuclear layer ( J:128315 , J:132497 )

• reduced in thickness by 6 months (J:128315)

• reduced overall at 12 months; layer is completely diminished by 24 months (J:132497)

retina outer nuclear layer degeneration ( J:132497 )

• destruction of ONL is seen starting at 6 months

nervous system

decreased retina photoreceptor cell number ( J:128315 , J:132497 )

• significant loss of photoreceptors is seen at 6 months, resulting in thinning of outer nuclear layer (J:128315)

• increased loss is detected at 12 months (J:132497)

retina photoreceptor degeneration ( J:132497 )

• observed at 10 months

cardiovascular system

choroidal neovascularization ( J:132497 )

• CNV membranes develop after 6 months of age with some tissue destruction in INL and ONL

• some retinal-choroidal anastomoses may be observed at 10 months

retina neovascularization ( J:128315 , J:132497 )

• new vessels form in outer plexiform layer of retina around 3 weeks of age; vessels migrate into subretinal space by 4 weeks (J:128315)

• angiography shows leakage in retinas at 6 weeks, mainly in central area of retina near optic nerve, with red blood cells found around the leakage spot; neovascularization is localized to outer nuclear layer and in subretinal space (J:128315)

• signs of new vessel growth is observed at 14 days in deep capillary bed of outer plexiform layer (OPL) of retina, protruding into avascular zone of outer nuclear layer (ONL) (J:132497)

• new vessel buds reach subretinal space by P15 (J:132497)

• leakage is first seen at 3 weeks and increases with age, with leaking areas covering most of retinal by 6 weeks (J:132497)

• clumps of retinal pigmented epithelial cells (RPE) adhere to neovascular tufts in subretinal space; these increase with age (J:132497)

• subretinal neovascularization (SRN) is seen at 6 weeks of age (J:132497)

• fibrosis formation is present at 12 months, beginning around 3 months with fibroblast accumulation at lesion site (J:132497)

pigmentation

abnormal retina pigment epithelium morphology ( J:128315 , J:132497 )

• thickening of RPE cells is observed prior to development of intraretinal neovascularization (J:128315)

• disruption of RPE layer is observed by 6 weeks of age (J:132497)

• pigment adhesions to neural tissue are seen by 6 weeks, representing pigment epithelium detachment (J:132497)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration 1		DOID:0110014	OMIM:603075	J:132497