All Phenotypes Pik3ca<tm1.1Rzl> MGI Mouse

increased body weight ( J:315599 )

• adult males show significantly increased body weight at 3-4 months of age

• however, body weight is normal in peripubertal males at P30

increased total body fat amount ( J:315599 )

• adult males exhibit increased levels of adiposity

abnormal white adipose tissue physiology ( J:315599 )

• white adipose tissue (WAT) mRNA levels of leptin are significantly increased in fasted peripubertal males

• WAT mRNA levels of TNF-alpha are significantly increased in nonfasted adult, but not in peripubertal, males

reproductive system phenotype ( J:315599 , J:315599 )

N	• in contrast to males, female mice are fertile (J:315599)
N	• adult males exhibit no differences in total sperm count per epididymis and sperm motility relative to controls (J:315599) • testicular histology is grossly normal at P30 (J:315599) • no defects in spermatogenesis are observed in adult testes (J:315599)

abnormal anogenital distance ( J:315599 )

• anogenital distance is significantly reduced at P23 and remains shorter than in controls at P31

decreased testis weight ( J:315599 )

• testis weight is significantly reduced at P30

• however, testis weight is normal in adult males

abnormal testis physiology ( J:315599 )

• mRNA levels of leptin are significantly increased in peripubertal and adult testes

• mRNA levels of Star (encoding steroidogenic acute regulatory protein) and of genes encoding steroidogenic enzymes such as Cyp11a1 (aka P450scc) and Cyp19 (aka aromatase) are significantly reduced in peripubertal testes but relatively unaffected in adult testes

• mRNA levels of 17-beta-dehydrogenase 3 (Hsd17b3), but not of Cyp17a1, are significantly increased in adult testes

• mRNA levels of estrogen receptor alpha (Esr1) are significantly decreased in both peripubertal and adult testes

• however, mRNA levels of leptin, insulin and androgen receptors (Lepr, Insr and Ar, respectively) are normal in both P30 and adult testes

delayed sexual maturation ( J:315599 )

• males exhibit delayed onset of puberty

delayed balanopreputial separation ( J:315599 )

• onset of balanopreputial separation is delayed, occurring ~3 days later than in controls

male infertility ( J:315599 )

• adult males failed to sire any pups after mating with a fertile female for 7 days

homeostasis/metabolism phenotype ( J:315599 )

N	• adult males exhibit normal basal LH, FSH, and estradiol levels • plasma FSH levels are lower but NOT significantly reduced at P30

abnormal hormone level ( J:315599 )

• WAT mRNA levels of leptin are significantly increased in fasted peripubertal males

• testicular mRNA levels of leptin are significantly increased in peripubertal and adult males

abnormal circulating androgen level ( J:315599 )

• adult males exhibit hyperandrogenemia

increased circulating testosterone level ( J:315599 )

• plasma testosterone levels are significantly increased in adult males

• however, plasma testosterone levels are normal at P30

decreased circulating luteinizing hormone level ( J:315599 )

• males show significantly reduced plasma LH levels at P30

increased circulating leptin level ( J:315599 )

• fasted plasma leptin levels are significantly increased in both peripubertal (P30) and adult (3- to 4-mo-old) males