Phenotypes associated with this allele

• Allele Symbol: Pik3ca^tm1.1Waph
• Allele Name: targeted mutation 1.1, Wayne A Phillips
• Allele ID: MGI:5427579
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pik3ca^tm1.1Waph/Pik3ca^+	involves: 129S1/Sv * C57BL/6	MGI:5427584
cn2	Pik3ca^tm1.1Waph/Pik3ca^+ Tg(MMTV-cre)#Mam/0	involves: 129S1/Sv * C57BL/6 * FVB	MGI:5755852
cx3	Pik3ca^tm1.1Waph/Pik3ca^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * BALB/c * C57BL/6	MGI:5427585

Genotype
MGI:5427584

cn1

• Allelic Composition: Pik3ca^tm1.1Waph/Pik3ca⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

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

Hyperproliferation of the ovarian surface epithelium in Pik3ca^tm1.1Waph/Pik3ca^tm1.1Waph mice

cellular

decreased fibroblast apoptosis ( J:184382 )

• in mouse embryonic fibroblasts after cre-expressing adenovirus infection

increased fibroblast proliferation ( J:184382 )

• in mouse embryonic fibroblasts after cre-expressing adenovirus infection

reproductive system

abnormal ovary morphology ( J:184382 )

♀ • the ovarian surface epithelium of mice infected with a cre-expressing adenovirus exhibit mild, focal papillary serous hyperplasia compared with control mice

endocrine/exocrine glands

abnormal ovary morphology ( J:184382 )

♀ • the ovarian surface epithelium of mice infected with a cre-expressing adenovirus exhibit mild, focal papillary serous hyperplasia compared with control mice

Genotype
MGI:5755852

cn2

• Allelic Composition: Pik3ca^tm1.1Waph/Pik3ca⁺; Tg(MMTV-cre)#Mam/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * FVB

mortality/aging

premature death ( J:187299 )

♀ • nulliparous mice show a median tumor-free survival of 484 days, while biparous mice show a median tumor-free survival of 393 days

endocrine/exocrine glands

increased mammary gland epithelial cell proliferation ( J:187299 )

♀ • increase in proliferation within the multilayered epithelia of the mammary ducts

♀ • colony forming ability of the luminal progenitors is enhanced

abnormal mammary gland epithelium morphology ( J:187299 )

♀ • loss of polarity in the mammary gland epithelium

♀ • the luminal cell population (Lin-CD29loCD24+) and luminal progenitors (Lin-CD29loCD24+CD61+) are increased in 6 week old mice

abnormal mammary gland duct morphology ( J:187299 )

♀ • mammary gland ducts are dilated at both 6 and 12 weeks of age and the majority at 12 weeks are enlarged and show areas of multilayered epithelium which is hyperplastic in some regions and shows presence of an eosinophilic luminal secretion

♀ • 13 month old nulliparous and biparous mice show enlarged ducts, particularly in the nipple region of the biparous mice and small focal lesions

♀ • mammary glands of aged mice have ectatic ducts filled with eosinophilic luminal secretions

abnormal branching of the mammary ductal tree ( J:187299 )

♀ • mice show increased secondary and tertiary branching at 12 weeks of age

abnormal mammary duct terminal end bud morphology ( J:187299 )

♀ • mice show increased number and size of invading mammary gland terminal end buds at 6 weeks

♀ • increase in proliferation within the terminal end buds

abnormal mammary gland myoepithelium morphology ( J:187299 )

♀ • anaplasia of basal cells in the mammary gland

♀ • colony forming ability of the stem cell enriched basal population is enhanced

abnormal mammary gland stroma morphology ( J:187299 )

♀ • ducts are surrounded by an increase in the number of stromal cells

increased mammary gland tumor incidence ( J:187299 )

♀ • nulliparous and biparous mice over 12 months of age develop mammary gland tumors, with tumor formation accelerated in biparous mice

♀ • however, no metastasis is seen

increased fibroadenoma incidence ( J:187299 )

♀ • 45% of tumors are benign fibroadenomas

increased mammary adenoacanthoma incidence ( J:187299 )

♀ • 10% of mammary tumors are adenosquamous carcinomas

cellular

increased mammary gland epithelial cell proliferation ( J:187299 )

♀ • increase in proliferation within the multilayered epithelia of the mammary ducts

♀ • colony forming ability of the luminal progenitors is enhanced

integument

increased mammary gland epithelial cell proliferation ( J:187299 )

♀ • increase in proliferation within the multilayered epithelia of the mammary ducts

♀ • colony forming ability of the luminal progenitors is enhanced

abnormal mammary gland epithelium morphology ( J:187299 )

♀ • loss of polarity in the mammary gland epithelium

♀ • the luminal cell population (Lin-CD29loCD24+) and luminal progenitors (Lin-CD29loCD24+CD61+) are increased in 6 week old mice

abnormal mammary gland duct morphology ( J:187299 )

♀ • mammary gland ducts are dilated at both 6 and 12 weeks of age and the majority at 12 weeks are enlarged and show areas of multilayered epithelium which is hyperplastic in some regions and shows presence of an eosinophilic luminal secretion

♀ • 13 month old nulliparous and biparous mice show enlarged ducts, particularly in the nipple region of the biparous mice and small focal lesions

♀ • mammary glands of aged mice have ectatic ducts filled with eosinophilic luminal secretions

abnormal branching of the mammary ductal tree ( J:187299 )

♀ • mice show increased secondary and tertiary branching at 12 weeks of age

abnormal mammary duct terminal end bud morphology ( J:187299 )

♀ • mice show increased number and size of invading mammary gland terminal end buds at 6 weeks

♀ • increase in proliferation within the terminal end buds

abnormal mammary gland myoepithelium morphology ( J:187299 )

♀ • anaplasia of basal cells in the mammary gland

♀ • colony forming ability of the stem cell enriched basal population is enhanced

abnormal mammary gland stroma morphology ( J:187299 )

♀ • ducts are surrounded by an increase in the number of stromal cells

increased mammary gland tumor incidence ( J:187299 )

♀ • nulliparous and biparous mice over 12 months of age develop mammary gland tumors, with tumor formation accelerated in biparous mice

♀ • however, no metastasis is seen

increased fibroadenoma incidence ( J:187299 )

♀ • 45% of tumors are benign fibroadenomas

increased mammary adenoacanthoma incidence ( J:187299 )

♀ • 10% of mammary tumors are adenosquamous carcinomas

skeleton

increased osteosarcoma incidence ( J:187299 )

♀ • 2.5% of tumors are osteosarcoma

neoplasm

increased mammary gland tumor incidence ( J:187299 )

♀ • nulliparous and biparous mice over 12 months of age develop mammary gland tumors, with tumor formation accelerated in biparous mice

♀ • however, no metastasis is seen

increased fibroadenoma incidence ( J:187299 )

♀ • 45% of tumors are benign fibroadenomas

increased mammary adenoacanthoma incidence ( J:187299 )

♀ • 10% of mammary tumors are adenosquamous carcinomas

increased sarcoma incidence ( J:187299 )

♀ • 42.5% of mammary tumors are carcinosarcomas or sarcomas

increased osteosarcoma incidence ( J:187299 )

♀ • 2.5% of tumors are osteosarcoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:187299

Genotype
MGI:5427585

cx3

• Allelic Composition: Pik3ca^tm1.1Waph/Pik3ca⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * BALB/c * C57BL/6

Ovary tumors in Pik3ca^tm1.1Waph/Pik3ca^tm1.1Waph Pten^tm1Hwu/Pten^tm1Hwu mice

mortality/aging

premature death ( J:184382 )

• of mice infected with a cre-expressing adenovirus due to ovarian masses with a median latency of 16 weeks

• however, treatment with an ATP-competitive PI3K/mTOR inhibitor, PF04691502 extends survival time

reproductive system

abnormal ovary morphology ( J:184382 )

♀ • the ovarian surface epithelium of mice infected with a cre-expressing adenovirus exhibit marked hyperplasia compared with control mice

♀ • mice infected with a cre-expressing adenovirus exhibit ovarian masses and show varying degrees of fibrous and/or smooth muscle hyperplasia compared with control mice

increased ovary tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice

increased granulosa cell tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice

abnormal ovary physiology ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus exhibit ovarian surface epithelium hyperproliferative changes compared with control mice

ovary hemorrhage ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice

neoplasm

increased ovary tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice

increased granulosa cell tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice

increased adenocarcinoma incidence ( J:184382 )

• mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas compared with control mice

growth/size/body

abnormal peritoneum morphology ( J:184382 )

• mice infected with a cre-expressing adenovirus exhibit intraperitoneal masses on the peritoneal wall and diaphragm masses compared with control mice

homeostasis/metabolism

hemorrhagic ascites ( J:184382 )

• mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice

cardiovascular system

ovary hemorrhage ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice

endocrine/exocrine glands

abnormal ovary morphology ( J:184382 )

♀ • the ovarian surface epithelium of mice infected with a cre-expressing adenovirus exhibit marked hyperplasia compared with control mice

♀ • mice infected with a cre-expressing adenovirus exhibit ovarian masses and show varying degrees of fibrous and/or smooth muscle hyperplasia compared with control mice

increased ovary tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian serous adenocarcinomas, ovarian granulosa cell tumors and a single ovarian luteoma compared with control mice

increased granulosa cell tumor incidence ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop ovarian granulosa cell tumors compared with control mice

abnormal ovary physiology ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus exhibit ovarian surface epithelium hyperproliferative changes compared with control mice

ovary hemorrhage ( J:184382 )

♀ • mice infected with a cre-expressing adenovirus develop hemorrhagic ascites compared with control mice

muscle

abnormal diaphragm morphology ( J:184382 )

• mice infected with a cre-expressing adenovirus exhibit intraperitoneal masses on the peritoneal wall and diaphragm masses compared with control mice