Phenotypes associated with this allele

• Allele Symbol: Mpc1^{tm1c(EUCOMM)Wtsi}
• Allele Name: targeted mutation 1c, Wellcome Trust Sanger Institute
• Allele ID: MGI:5903307
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mpc1^tm1c(EUCOMM)Wtsi/Mpc1^tm1c(EUCOMM)Wtsi	involves: C57BL/6J * C57BL/6N	MGI:5903312
cn2	Mpc1^tm1c(EUCOMM)Wtsi/Mpc1^tm1c(EUCOMM)Wtsi Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA	MGI:5903311
cn3	Mpc1^tm1c(EUCOMM)Wtsi/Mpc1^tm1c(EUCOMM)Wtsi Tg(Six3-cre)69Frty/0	involves: C57BL/6N * DBA/2	MGI:6383176

Genotype
MGI:5903312

cn1

• Allelic Composition: Mpc1^{tm1c(EUCOMM)Wtsi}/Mpc1^{tm1c(EUCOMM)Wtsi}
• Genetic Background: involves: C57BL/6J * C57BL/6N

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

homeostasis/metabolism

improved glucose tolerance ( J:236662 )

• in mice infected with a cre-expressing adenovirus and fed a high-fat diet

increased insulin sensitivity ( J:236662 )

• in mice infected with a cre-expressing adenovirus and fed a high-fat diet

Genotype
MGI:5903311

cn2

• Allelic Composition: Mpc1^{tm1c(EUCOMM)Wtsi}/Mpc1^{tm1c(EUCOMM)Wtsi}; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:236662 )

N • mice exhibit normal alanine and aspartate transaminase levels, glucose and insulin tolerance

increased fatty acid oxidation ( J:236662 )

• hepatic and whole-body

decreased circulating glucose level ( J:236662 )

• after 9 weeks on a high-fat diet

increased circulating ketone body level ( J:236662 )

• in mice fed standard chow or a high-fat diet

increased circulating lactate level ( J:236662 )

• slightly in mice fed normal chow

• fasting lactate in mice fed a high-fat diet

decreased circulating cholesterol level ( J:236662 )

decreased circulating triglyceride level ( J:236662 )

• fasting

decreased respiratory quotient ( J:236662 )

• during the dark cycle when most physically active

abnormal gluconeogenesis ( J:236662 )

• impaired pyruvate-driven gluconeogenesis

• however, hepatic glycogen levels are normal

improved glucose tolerance ( J:236662 )

• in mice fed a high-fat diet

• however, insulin tolerance is the same as in controls

increased triglyceride level ( J:236662 )

• slightly increased postabsorptive triglycerides when fed normal chow

• increased postabsorptive triglycerides in mice fed a high-fat diet

• however, liver triglycerides are normal

cellular

abnormal mitochondrial physiology ( J:236662 )

• mitochondria exhibit a complete loss of pyruvate uptake compared with control mice

increased fatty acid oxidation ( J:236662 )

• hepatic and whole-body

growth/size/body

decreased body weight ( J:236662 )

• slightly

• however, body composition are normal

behavior/neurological

behavior/neurological phenotype ( J:236662 )

N • mice exhibit normal food intake and voluntary physical activity

Genotype
MGI:6383176

cn3

• Allelic Composition: Mpc1^{tm1c(EUCOMM)Wtsi}/Mpc1^{tm1c(EUCOMM)Wtsi}; Tg(Six3-cre)69Frty/0
• Genetic Background: involves: C57BL/6N * DBA/2

vision/eye

abnormal Muller cell morphology ( J:271892 )

• activated and disorganized Muller glial cells

abnormal retina photoreceptor morphology ( J:271892 )

• abnormal inner and outer segment junction layer caused by a shed portion of an ellipsoid region with swollen mitochondria and small vacuoles

abnormal photoreceptor inner segment morphology ( J:271892 )

• small vacuoles

abnormal photoreceptor outer segment disc membrane morphology ( J:271892 )

• at P30

short photoreceptor outer segment ( J:271892 )

• slight at P14 near the optic nerve

• at P20 with progressive decrease thereafter

thin retina inner plexiform layer ( J:271892 )

• at P30

thin retina outer nuclear layer ( J:271892 )

• at P20 with progressive decrease thereafter

retina degeneration ( J:271892 )

abnormal eye physiology ( J:271892 )

• reduced retinal lactate to pyruvate ratio

• blocked glucose oxidation in retinal mitochondria with accumulation of pyruvate and aspartate and reduced intermediates, especially glutamine

• enhanced consumption of ketone bodies in the retina

• decreased acylcarnitine indicating enhanced fatty acid oxidation in the retina

• accumulation of aspartate at the expense of glutamine in the retina

• reduced oxygen consumption rate in retinal mitochondria with reduced ATP and NADH at P30

abnormal cone electrophysiology ( J:271892 )

• impaired at P30 and remaining constant until P90

abnormal rod electrophysiology ( J:271892 )

• progressive decline in a-wave responses at P30, P60 and P90

• progressive decreased b-wave responses beginning at P20

• however, response at P20 is normal

homeostasis/metabolism

abnormal glucose homeostasis ( J:271892 )

• blocked glucose oxidation in retinal mitochondria with accumulation of pyruvate and aspartate and reduced intermediates, especially glutamine

abnormal metabolism ( J:271892 )

• increased pyruvate, aspartate and proline with decreased coenzyme A, 3-hydroxybutyrate, glutamate, glutamine and glutathione in the retina

• reduced retinal lactate to pyruvate ratio

• blocked glucose oxidation in retinal mitochondria with accumulation of pyruvate and aspartate and reduced intermediates, especially glutamine

• enhanced consumption of ketone bodies in the retina

• decreased acylcarnitine indicating enhanced fatty acid oxidation in the retina

• accumulation of aspartate at the expense of glutamine in the retina

• reduced oxygen consumption rate in retinal mitochondria with reduced ATP and NADH at P30

nervous system

abnormal Muller cell morphology ( J:271892 )

• activated and disorganized Muller glial cells

abnormal retina photoreceptor morphology ( J:271892 )

• abnormal inner and outer segment junction layer caused by a shed portion of an ellipsoid region with swollen mitochondria and small vacuoles

abnormal photoreceptor inner segment morphology ( J:271892 )

• small vacuoles

abnormal photoreceptor outer segment disc membrane morphology ( J:271892 )

• at P30

short photoreceptor outer segment ( J:271892 )

• slight at P14 near the optic nerve

• at P20 with progressive decrease thereafter