Phenotypes Associated with This Genotype

Genotype
MGI:6389045

• Allelic Composition: Ppargc1a^tm1Brsp/Ppargc1a⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

vision/eye

abnormal choroid vasculature morphology ( J:264271 )

• mice fed a regular diet show enlarged blood vessels in the interface between the Bruch's membrane and the choroid, with congestion and dilatation of some vessels

abnormal choriocapillaris morphology ( J:264271 )

• mice fed a high-fat diet show a greater loss of fenestration in choriocapillaris endothelium

short photoreceptor inner segment ( J:264271 )

• mice fed a regular diet and a high-fat diet show a reduction of thickness of the inner segment layer

short photoreceptor outer segment ( J:264271 )

• mice fed a regular diet and a high-fat diet show a reduction of thickness of the outer segment layer

retina photoreceptor degeneration ( J:264271 )

• mice fed a high-fat diet exhibit a thinner photoreceptor layer, indicating degeneration of this layer

• photoreceptor degeneration does not necessarily initiate concurrently in both eyes

abnormal retina pigment epithelium morphology ( J:264271 )

• mice fed a regular diet show higher numbers of lipofuscin deposits in the retinal pigment epithelium (RPE) than wild-type mice

• mice fed a high-fat diet show a greater accumulation of lipofuscin in the cytoplasm of the RPE, basal laminar deposits, and thickening of the outer collagenous layer

• mice fed a high-fat diet show RPE retinal pigment epithelium degeneration, with disruptions or gaps and scant melanosomes in the subretinal space migrating into the outer segment

retina macular degeneration ( J:264271 )

• mice fed a high-fat diet present age-related macular degeneration-like abnormalities in the retinal pigment epithelium and retinal morphology and function

abnormal Bruch membrane morphology ( J:264271 )

• mice fed a high-fat diet show changes in the Bruch membrane, either atrophy or thickening in various regions

• mice fed a high-fat diet show accumulation of carboxymethyl lysine (CML) deposits in the thickened Bruch membrane, indicating oxidative damage

immune system

increased inflammatory response ( J:264271 )

• lipopolysaccharide (LPS) injection induces a higher inflammatory response in the retinal pigment epithelium (RPE)/retina compared to in wild-type mice

cardiovascular system

abnormal choroid vasculature morphology ( J:264271 )

• mice fed a regular diet show enlarged blood vessels in the interface between the Bruch's membrane and the choroid, with congestion and dilatation of some vessels

abnormal choriocapillaris morphology ( J:264271 )

• mice fed a high-fat diet show a greater loss of fenestration in choriocapillaris endothelium

homeostasis/metabolism

impaired autophagy ( J:264271 )

• autophagy is reduced in the retinal pigment epithelium/retina

nervous system

short photoreceptor inner segment ( J:264271 )

• mice fed a regular diet and a high-fat diet show a reduction of thickness of the inner segment layer

short photoreceptor outer segment ( J:264271 )

• mice fed a regular diet and a high-fat diet show a reduction of thickness of the outer segment layer

retina photoreceptor degeneration ( J:264271 )

• mice fed a high-fat diet exhibit a thinner photoreceptor layer, indicating degeneration of this layer

• photoreceptor degeneration does not necessarily initiate concurrently in both eyes

pigmentation

abnormal retina pigment epithelium morphology ( J:264271 )

• mice fed a regular diet show higher numbers of lipofuscin deposits in the retinal pigment epithelium (RPE) than wild-type mice

• mice fed a high-fat diet show a greater accumulation of lipofuscin in the cytoplasm of the RPE, basal laminar deposits, and thickening of the outer collagenous layer

• mice fed a high-fat diet show RPE retinal pigment epithelium degeneration, with disruptions or gaps and scant melanosomes in the subretinal space migrating into the outer segment

abnormal melanosome transport ( J:264271 )

• mice fed a high-fat diet show scant melanosomes migrating into the outer segment

lipofuscinosis ( J:264271 )

• mice fed a regular diet show higher numbers of lipofuscin deposits than wild-type mice

• mice fed a high-fat diet show a greater accumulation of lipofuscin in the cytoplasm of the RPE

cellular

decreased mitochondrial DNA content ( J:264271 )

• mice fed a high-fat diet show a greater decrease in mtDNA copy number than wild-type mice

impaired autophagy ( J:264271 )

• autophagy is reduced in the retinal pigment epithelium/retina

abnormal mitochondrial physiology ( J:264271 )

• mice fed a high-fat diet show a greater decrease in mitochondrial complex I activity in the retinal pigment epithelium/retina

oxidative stress ( J:264271 )

• mice fed a high-fat diet show accumulation of carboxymethyl lysine deposits in the thickened Bruchs membrane, indicating oxidative damage

• mice fed a high-fat diet show increased reactive oxygen species (ROS) levels in the retinal pigment epithelium/retina

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration		DOID:10871	OMIM:PS603075	J:264271