Phenotypes Associated with This Genotype

Genotype
MGI:6197269

• Allelic Composition: Gt(ROSA)26Sor^{tm7(Pik3ca*,EGFP)Rsky}/Gt(ROSA)26Sor⁺; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: B6.Cg-Gt(ROSA)26Sor^{tm7(Pik3ca*,EGFP)Rsky} Tg(CAG-cre/Esr1*)5Amc

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

mortality/aging

premature death ( J:264410 )

• mice administered a single low dose (4 mg/kg) of tamoxifen to induce cre recombination survive 2 months and then die with multiple abnormalities

• tamoxifen-administered mice treated with rapamycin show improved survival but no improvement in organ abnormalities such as liver and spleen disorganization with aberrant vascularization

postnatal lethality, incomplete penetrance ( J:264410 )

• mice start to rapidly die after 40 mg/kg tamoxifen administration, with 50% of mortality at day 9

• tamoxifen-administered mice treated with BYL719 are alive after 40 days, however interruption of BYL719 treatment 40 days after tamoxifen-administration leads to rapid death

• tamoxifen-administered mice treated with rapamycin show improved survival but no improvement in organ abnormalities such as liver and spleen disorganization with aberrant vascularization

growth/size/body

kidney cyst ( J:264410 )

• kidney cysts in tamoxifen-administered mice

visceromegaly ( J:264410 )

• organomegaly is seen in mice administered a single low dose of tamoxifen

cardiovascular system

abnormal blood vessel morphology ( J:264410 )

• vessel abnormalities in tamoxifen-administered mice

• tamoxifen-administered mice treated with BYL719 show normal vessels

abnormal vein morphology ( J:264410 )

• ecstatic venous channels with a thin endothelial cell lining, surrounded by sparse, erratically distributed vascular smooth muscle cells and a disorganized extracellular matrix are seen in mice administered a low dose of tamoxifen

dilated vasculature ( J:264410 )

• severe vessel dilation in tamoxifen-administered mice

internal hemorrhage ( J:264410 )

• intra-abdominal hemorrhages in tamoxifen-administered mice

liver hemorrhage ( J:264410 )

• hepatic hemorrhages in tamoxifen-administered mice

cellular

increased cell proliferation ( J:264410 )

• high number of proliferating cells in affected organs of tamoxifen-administered mice

• however, no changes in apoptosis are seen

• tamoxifen-administered mice treated with BYL719 show a reduction in proliferation

hematopoietic system

abnormal spleen morphology ( J:264410 )

• loss of spleen microarchitecture integrity in tamoxifen-administered mice

immune system

abnormal spleen morphology ( J:264410 )

• loss of spleen microarchitecture integrity in tamoxifen-administered mice

enlarged lymphatic vessel ( J:264410 )

• expansion of lymphatic vessels in tamoxifen-administered mice

limbs/digits/tail

abnormal limb morphology ( J:264410 )

• mice administered a single low dose of tamoxifen progressively develop asymmetrical overgrowth of extremities, disseminated voluminous tumors and subcutaneous vascular abnormalities

• low-dose tamoxifen administered mice treated with BYL719 show improvement of the overgrowth of extremities, however, withdrawal of BYL719 leads to the development of asymmetric extremity hypertrophy within 4 weeks

liver/biliary system

liver hemorrhage ( J:264410 )

• hepatic hemorrhages in tamoxifen-administered mice

hepatic steatosis ( J:264410 )

• severe liver steatosis with vessel disorganization in tamoxifen-administered mice

muscle

skeletal muscle hypertrophy ( J:264410 )

• muscle hypertrophy in tamoxifen-administered mice

• mice treated with BYL719 7 days after cre induction show improved muscle hypertrophy

neoplasm

increased classified tumor incidence ( J:264410 )

• low dose tamoxifen-administered mice develop tumors that are lipomatous tumors and severe vascular lesions mixing venous and arterial vessels

• low-dose tamoxifen administered mice treated with BYL719 show reduced and disappearance of visible tumors within 2 weeks

• withdrawal of BYL719 from the low-dose tamoxifen administered mice leads to recurrence of tumors

• low-dose tamoxifen-administered mice treated with rapamycin show no effect on tumor growth

renal/urinary system

kidney cyst ( J:264410 )

• kidney cysts in tamoxifen-administered mice

renal fibrosis ( J:264410 )

• fibrosis of the kidney with aberrant vessels in tamoxifen-administered mice

skeleton

scoliosis ( J:264410 )

• scoliosis in tamoxifen-administered mice

• mice treated with BYL719 7 days after cre induction show improved scoliosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CLOVES syndrome		DOID:0080351	OMIM:612918	J:264410