Phenotypes associated with this allele

• Allele Symbol: Pik3ca⁺
• Allele Name: wild type
• Allele ID: MGI:2435219
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Pik3ca^tm1Bvan/Pik3ca^+	involves: 129P2/OlaHsd	MGI:3796331
ht2	Pik3ca^tm1Bvan/Pik3ca^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3629699
ht3	Pik3ca^tm1Gilb/Pik3ca^+	Not Specified	MGI:5438216
cn4	Pik3ca^tm1.1Waph/Pik3ca^+	involves: 129S1/Sv * C57BL/6	MGI:5427584
cn5	Ctnnb1^tm1Mmt/Ctnnb1^+ Pik3ca^tm1Gilb/Pik3ca^+ Trp53^tm1Brn/Trp53^+ Tg(Fabp7-cre,-lacZ)3Gtm/0	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * CBA	MGI:5438217
cn6	Pik3ca^tm1.1Waph/Pik3ca^+ Tg(MMTV-cre)#Mam/0	involves: 129S1/Sv * C57BL/6 * FVB	MGI:5755852
cn7	Pik3ca^tm1Gne/Pik3ca^+ Tg(MMTV-cre)1Mam/0	involves: C57BL/6N * FVB/N	MGI:5469591
cx8	Pik3ca^tm1.1Waph/Pik3ca^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * BALB/c * C57BL/6	MGI:5427585
cx9	Pik3ca^tm1Nbm/Pik3ca^+ Pik3cb^tm1Nbm/Pik3cb^+	involves: 129S6/SvEvTac	MGI:2651931

Genotype
MGI:3796331

ht1

• Allelic Composition: Pik3ca^tm1Bvan/Pik3ca⁺
• Genetic Background: involves: 129P2/OlaHsd

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

cardiovascular system

abnormal retina vasculature morphology ( J:136236 )

• at P5, outgrowth of the primary vascular plexus in the retina is delayed compared to in wild-type mice

• however, endothelial cell proliferation and survival is normal

abnormal angiogenesis ( J:136236 )

• at E11.5, angiogenesis in the hindbrain is delayed compared to in wild-type mice

• at P5, outgrowth of the primary vascular plexus in the retina is delayed compared to in wild-type mice

vision/eye

abnormal retina vasculature morphology ( J:136236 )

• at P5, outgrowth of the primary vascular plexus in the retina is delayed compared to in wild-type mice

• however, endothelial cell proliferation and survival is normal

Genotype
MGI:3629699

ht2

• Allelic Composition: Pik3ca^tm1Bvan/Pik3ca⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

growth/size/body

decreased lean body mass ( J:109024 )

• lean mass determined by DEXA analysis are decreased compared to wild-type control

• major internal organ weight was not altered

decreased body weight ( J:109024 )

• throughout adult period compared to wild-type control of the same sex

decreased body length ( J:109024 )

• decreased mouth-to-anus length of 6-weeks old mice

postnatal growth retardation ( J:109024 )

• starts during embryonic development

fetal growth retardation ( J:109024 )

• reduced weight and crown-to-rump length of E18.5 embryos compared to wild-type control

homeostasis/metabolism

increased circulating insulin level ( J:109024 )

• when fasted or during a glucose tolerance test

increased circulating leptin level ( J:109024 )

♂ • significant increase in 5-week-old and 12-week-old male

impaired glucose tolerance ( J:109024 )

♀ • impaired glucose clearance during glucose tolerance test in female

♀ • fasting blood glucose levels were equivalent ot those of wild-type mice

insulin resistance ( J:109024 )

• an impaired hypoglycemic response to insulin

endocrine/exocrine glands

increased pancreatic beta cell number ( J:109024 )

behavior/neurological

polyphagia ( J:109024 )

• increased food intake in 12-week-old mice

adipose tissue

increased fat cell size ( J:109024 )

• enlarged white adipose cells

• increased fat mass and adipocyte number

muscle

decreased skeletal muscle mass ( J:109024 )

• reduced skeletal muscle mass

Genotype
MGI:5438216

ht3

• Allelic Composition: Pik3ca^tm1Gilb/Pik3ca⁺
• Genetic Background: Not Specified

neoplasm

neoplasm ( J:186709 )

N • mice do not develop medulloblastomas

Genotype
MGI:5427584

cn4

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

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:5438217

cn5

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Pik3ca^tm1Gilb/Pik3ca⁺; Trp53^tm1Brn/Trp53⁺; Tg(Fabp7-cre,-lacZ)3Gtm/0
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * CBA

neoplasm

increased medulloblastoma incidence ( J:186709 )

• by 3 months of age, all mice develop WNT-subgroup medulloblastomas

nervous system

increased medulloblastoma incidence ( J:186709 )

• by 3 months of age, all mice develop WNT-subgroup medulloblastomas

Genotype
MGI:5755852

cn6

• 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:5469591

cn7

• Allelic Composition: Pik3ca^tm1Gne/Pik3ca⁺; Tg(MMTV-cre)1Mam/0
• Genetic Background: involves: C57BL/6N * FVB/N

neoplasm

neoplasm ( J:193377 )

♂N • male mice do not develop tumors in the mammary gland or seminal vesicles

increased mammary gland tumor incidence ( J:193377 )

♀ • thoracic and inguino-abdominal mammary gland tumors with latency dependent on nulliparous or multiparous condition

♀ • however, treatment with PI3K inhibitor inhibits tumor growth

integument

abnormal branching of the mammary ductal tree ( J:193377 )

♀ • precocious lobulo-alveolar development and hyper-branched ductal structures (2-fold increase in ductal branch point) at 12 weeks

♀ • feathery, hyper-branched ductal tree by 50 weeks

increased mammary gland tumor incidence ( J:193377 )

♀ • thoracic and inguino-abdominal mammary gland tumors with latency dependent on nulliparous or multiparous condition

♀ • however, treatment with PI3K inhibitor inhibits tumor growth

endocrine/exocrine glands

abnormal branching of the mammary ductal tree ( J:193377 )

♀ • precocious lobulo-alveolar development and hyper-branched ductal structures (2-fold increase in ductal branch point) at 12 weeks

♀ • feathery, hyper-branched ductal tree by 50 weeks

increased mammary gland tumor incidence ( J:193377 )

♀ • thoracic and inguino-abdominal mammary gland tumors with latency dependent on nulliparous or multiparous condition

♀ • however, treatment with PI3K inhibitor inhibits tumor growth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:193377

Genotype
MGI:5427585

cx8

• 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

Genotype
MGI:2651931

cx9

• Allelic Composition: Pik3ca^tm1Nbm/Pik3ca⁺; Pik3cb^tm1Nbm/Pik3cb⁺
• Genetic Background: involves: 129S6/SvEvTac

homeostasis/metabolism

increased circulating insulin level ( J:96761 )

• mild hyperinsulinemia in the fasted state at 6 months of age

impaired glucose tolerance ( J:96761 )

• mild glucose intolerance in glucose tolerance test at 6 months of age but not at early ages

• however, no differences seen in glucose clearance during an insulin tolerance test