Phenotypes associated with this allele

• Allele Symbol: Ppargc1a⁺
• Allele Name: wild type
• Allele ID: MGI:2437928
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Ppargc1a^tm1Aztc/Ppargc1a^+	C57BL/6-Ppargc1a^tm1Aztc	MGI:5882334
ht2	Ppargc1a^tm1Brsp/Ppargc1a^+	involves: 129 * FVB/N	MGI:5576901
ht3	Ppargc1a^tm1Brsp/Ppargc1a^+	involves: 129S4/SvJae * C57BL/6	MGI:6389045
cn4	Ppargc1a^tm2Brsp/Ppargc1a^+ Tg(Myog-cre)1Eno/0	involves: 129 * C57BL/6	MGI:5576900
cx5	Htt^tm1Mfc/Htt^+ Ppargc1a^tm1Dpk/Ppargc1a^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3698750
cx6	Mirc33^tm1.1Wtsi/Mirc33^tm1.1Wtsi Ppargc1a^tm1Brsp/Ppargc1a^+	involves: 129S4/SvJae * C57BL/6N	MGI:6367623

Genotype
MGI:5882334

ht1

• Allelic Composition: Ppargc1a^tm1Aztc/Ppargc1a⁺
• Genetic Background: C57BL/6-Ppargc1a^tm1Aztc

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

adipose tissue

decreased retroperitoneal fat pad weight ( J:82809 )

• significantly decreased

growth/size/body

decreased lean body mass ( J:82809 )

♂ • significantly decreased

decreased body weight ( J:82809 )

♂ • significantly decreased

decreased body length ( J:82809 )

♂ • significantly decreased

increased kidney weight ( J:82809 )

• significantly increased

skeleton

decreased bone mineral content ( J:82809 )

♂ • significantly decreased

behavior/neurological

decreased food intake ( J:82809 )

endocrine/exocrine glands

increased adrenal gland weight ( J:82809 )

• significantly increased

increased thymus weight ( J:82809 )

• significantly increased

hematopoietic system

increased thymus weight ( J:82809 )

• significantly increased

thrombocytopenia ( J:82809 )

• heterozygous mutant mice exhibit lower platelet counts than their wild-type littermates

homeostasis/metabolism

decreased circulating cholesterol level ( J:82809 )

• heterozygous mutant mice exhibit lower total plasma cholesterol than their wild-type littermates

increased circulating alkaline phosphatase level ( J:82809 )

decreased respiratory quotient ( J:82809 )

• heterozygous mutant mice have a lower respiratory exchange ratio (RER) than their wild-type littermates

immune system

increased thymus weight ( J:82809 )

• significantly increased

renal/urinary system

increased kidney weight ( J:82809 )

• significantly increased

Genotype
MGI:5576901

ht2

• Allelic Composition: Ppargc1a^tm1Brsp/Ppargc1a⁺
• Genetic Background: involves: 129 * FVB/N

immune system

immune system phenotype ( J:127403 )

N • mice exhibit normal serum IL6 levels

Genotype
MGI:6389045

ht3

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

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

Genotype
MGI:5576900

cn4

• Allelic Composition: Ppargc1a^tm2Brsp/Ppargc1a⁺; Tg(Myog-cre)1Eno/0
• Genetic Background: involves: 129 * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:127403 )

N • mice fed a high fat diet exhibit normal heat production and oxygen consumption

increased circulating glucose level ( J:127403 )

• in mice fed a high fat diet

• however, mice fed standard chow exhibit normal glucose serum levels

increased circulating interleukin-6 level ( J:127403 )

impaired glucose tolerance ( J:127403 )

• in mice fed standard chow or a high fat diet

immune system

increased circulating interleukin-6 level ( J:127403 )

behavior/neurological

behavior/neurological phenotype ( J:127403 )

N • mice fed a high fat diet exhibit normal food intake

growth/size/body

growth/size/body region phenotype ( J:127403 )

N • mice fed standard chow or a high fat diet exhibit normal body weight and composition

Genotype
MGI:3698750

cx5

• Allelic Composition: Htt^tm1Mfc/Htt⁺; Ppargc1a^tm1Dpk/Ppargc1a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

behavior/neurological

impaired coordination ( J:116058 )

• rotarod performance is severely impaired and much worse than in mice carrying the Hdh^tm1Mfc knock-in allele

nervous system

abnormal striatum morphology ( J:116058 )

• striatal neuronal volumes are significantly decreased in 6-month old mutants compared to mice carrying the Hdh^tm1Mfc knock-in allele

neuron degeneration ( J:116058 )

• early neuronal degeneration appears in the striatum and the medial septal nucleus by 3 months of age

• mutants exhibit increased susceptibility to 3-nitropropionic acid, developing larger striatal lesions and increased number of degenerating neurons compared to mice carrying the Hdh^tm1Mfc knock-in allele

Genotype
MGI:6367623

cx6

• Allelic Composition: Mirc33^tm1.1Wtsi/Mirc33^tm1.1Wtsi; Ppargc1a^tm1Brsp/Ppargc1a⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6N

mortality/aging

premature death ( J:267719 )

• mice exhibit a life span extension compared with single Mirc33^tm1.1Wtsi homozygotes, with a median of 39.5 weeks compared to 30 weeks, but reduced survival compared to wild-type mice

cellular

decreased mitochondrial size ( J:267719 )

• cardiac mitochondrial size is smaller

• however, cardiac mitochondrial DNA levels and mitochondrial numbers are restored to wild-type levels

cardiovascular system

cardiovascular system phenotype ( J:267719 )

N • mice show a reduction in systemic blood pressure compared to single Mirc33^tm1.1Wtsi homozygotes