Phenotypes Associated with This Genotype

Genotype
MGI:8268434

• Allelic Composition: Gt(ROSA)26Sor^{tm7(Pik3ca*,-EGFP)Rsky}/Gt(ROSA)26Sor⁺; Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺; Tg(ACTA1-cre/Esr1*)2Kesr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6J

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

growth/size/body

abnormal body weight ( J:370764 )

• mice administered alpelisib, a PIK3CA inhibitor, daily starting 48 hours after cre induction (preventative alpelisib) exhibit a normal appearance during the 22 weeks of treatment and a body weight increase similar to that of controls

• mice administered alpelisib 2 weeks after cre induction when global muscle hypertrophy is already prominent for 20 additional weeks (therapeutic alpelisib), show a rapid body weight decrease

• 6-week-old mice treated with tamoxifen for 5 days show progressive weight gain starting at 3 weeks after treatment which is not seen in wild-type mice and around 11 weeks after induction in males and 24 weeks in females, body weight becomes lower than in wild-type mice

muscle

abnormal skeletal muscle fiber mitochondrial morphology ( J:370764 )

• mitochondrial mass is reduced in striated muscle cells of tamoxifen-treated mice

skeletal muscle hypertrophy ( J:370764 )

• mice show skeletal muscle hypertrophy at 15 weeks after tamoxifen, with hypertrophic striated cells

• mice administered alpelisib, a PIK3CA inhibitor, daily starting 48 hours after cre induction (preventative alpelisib) exhibit no skeletal muscle overgrowth 8 weeks after alpelisib initiation indicating that alpelisib prevents skeletal muscle overgrowth

• mice treated with therapeutic alpelisib show a reduction in muscular volume and striated muscle is conserved indicating that alpelisib reverses skeletal muscle overgrowth

abnormal muscle physiology ( J:370764 )

• striated muscle cells from tamoxifen-treated mice show an alteration in the mitochondrial transmembrane potential

increased muscle cell glucose uptake ( J:370764 )

• tamoxifen-treated mice show higher fluoro-D-glucose muscular uptake

adipose tissue

decreased total body fat amount ( J:370764 )

• tamoxifen-treated mice show reduced fat content

behavior/neurological

increased grip strength ( J:370764 )

• tamoxifen-treated mice show a gain in muscle strength

cellular

abnormal skeletal muscle fiber mitochondrial morphology ( J:370764 )

• mitochondrial mass is reduced in striated muscle cells of tamoxifen-treated mice

increased muscle cell glucose uptake ( J:370764 )

• tamoxifen-treated mice show higher fluoro-D-glucose muscular uptake

abnormal mitochondrial physiology ( J:370764 )

• striated muscle cells from tamoxifen-treated mice show an alteration in the mitochondrial transmembrane potential

homeostasis/metabolism

abnormal blood homeostasis ( J:370764 )

• plasma metabolites metabolomics analysis of tamoxifen-treated mice show metabolic changes with increases in acetyl-aspartate, acetyl-glutamine, acetyl-lysine, aminoadipate, ATP, camosine, citrate, creatinine, cytidine, decanoic acid, dodecanoyl-carnitine, dodecanoic acid/lauric acid, docosahexaenoic acid, hexanoic acid, hexanoyl-carnitine, linoleic acid, linolenic acid, methyl-lysine, myristic acid, myristoyl-carnitine, octanoyl-carnitine, oleic acid, O-phosphoethanolamine, palmitic acid, palmitoyl-carnitine, palmitoleic acid, phosphocreatine, riboflavin, S-adenosyl-L-homocysteine, and taurine, and decreases in glutamate, glucose, L-alanine, lysine, methionine, ornithine, threonine, tryptophan, and tyrosine

• alpelisib treatment results in partial correction of the different metabolic anomalies

hypoglycemia ( J:370764 )

• tamoxifen-treated mice are hypoglycemic

• mice treated with preventative alpelisib show normal 12-h fasted glycemia

• mice treated with therapeutic alpelisib show increased blood glucose levels

decreased circulating insulin level ( J:370764 )

• mice treated with therapeutic alpelisib show increased insulin levels

• however, mice show conserved insulin secretion in the oral glucose tolerance test

• mice treated with preventative alpelisib show corrected circulating insulin levels

• tamoxifen-treated mice exhibit low insulin levels

decreased circulating insulin-like growth factor I level ( J:370764 )

• tamoxifen-treated mice show low IGF1 levels

• mice treated with preventative alpelisib show corrected IGF1 levels

• mice treated with therapeutic alpelisib show increased circulating IGF1 levels