Phenotypes associated with this allele

• Allele Symbol: Pik3cb^tm1.1Ehi
• Allele Name: targeted mutation 1.1, Emilio Hirsch
• Allele ID: MGI:4358053
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi	B6.129P2-Pik3cb^tm1.1Ehi	MGI:4358062
hm2	Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi	involves: 129P2/OlaHsd	MGI:4358067
hm3	Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi	involves: 129/Sv * 129P2/OlaHsd * BALB/c * C57BL/6J	MGI:4358061
hm4	Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi	involves: 129/Sv * 129P2/OlaHsd * C57BL/6J	MGI:6856717
cx5	Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi Tg(MMTVneu)202Mul/0	involves: 129/Sv * 129P2/OlaHsd * BALB/c * C57BL/6J * FVB/N	MGI:4358063

Genotype
MGI:4358062

hm1

• Allelic Composition: Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi
• Genetic Background: B6.129P2-Pik3cb^tm1.1Ehi

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

homeostasis/metabolism

increased insulin secretion ( J:152332 )

• after 6 months

increased circulating glucose level ( J:152332 )

• after 6 months

impaired gluconeogenesis ( J:152332 )

• insulin-mediated gluconeogenesis is impaired

decreased liver glycogen level ( J:152332 )

• decreased glycogen level in the liver at 24 weeks

insulin resistance ( J:152332 )

• mild after 6 months

liver/biliary system

decreased liver glycogen level ( J:152332 )

• decreased glycogen level in the liver at 24 weeks

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:152332 )

• after 6 months

increased insulin secretion ( J:152332 )

• after 6 months

Genotype
MGI:4358067

hm2

• Allelic Composition: Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi
• Genetic Background: involves: 129P2/OlaHsd

hematopoietic system

abnormal platelet physiology ( J:152267 )

• platelet adhesion and spreading is reduced compared to in wild-type cells

• platelet spreading on fibrinogen is almost completely abolished unlike for wild-type cells

decreased platelet aggregation ( J:152267 )

• adenosine 5'-diphosphate (ADP)-induced platelet aggregation is impaired unlike in similarly treated wild-type cells

• when treated with U46619, platelet aggregation is impaired 30% compared to in similarly treated wild-type cells

• convulxin-induced aggregation is almost completely abolished compared to in similarly treated wild-type cells

homeostasis/metabolism

abnormal platelet physiology ( J:152267 )

• platelet adhesion and spreading is reduced compared to in wild-type cells

• platelet spreading on fibrinogen is almost completely abolished unlike for wild-type cells

decreased platelet aggregation ( J:152267 )

• adenosine 5'-diphosphate (ADP)-induced platelet aggregation is impaired unlike in similarly treated wild-type cells

• when treated with U46619, platelet aggregation is impaired 30% compared to in similarly treated wild-type cells

• convulxin-induced aggregation is almost completely abolished compared to in similarly treated wild-type cells

Genotype
MGI:4358061

hm3

• Allelic Composition: Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * BALB/c * C57BL/6J

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:152332 )

• 50% fewer than expected mice are born

embryonic lethality during organogenesis, incomplete penetrance ( J:152332 )

• 30% of mice are moribund at E13.5

growth/size/body

decreased embryo size ( J:152332 )

• in 30% of mice at E13.5

decreased birth body size ( J:152332 )

postnatal growth retardation ( J:152332 )

• 20% until 24 weeks of age

homeostasis/metabolism

decreased circulating cholesterol level ( J:152332 )

decreased circulating triglyceride level ( J:152332 )

cellular

decreased fibroblast proliferation ( J:152332 )

• mouse embryonic fibroblasts with low expression of the allele exhibit decreased proliferation compared with wild-type cells

• however, MEFs expressing high levels of the allele exhibit normal proliferation

embryo

decreased embryo size ( J:152332 )

• in 30% of mice at E13.5

Genotype
MGI:6856717

hm4

• Allelic Composition: Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6J

reproductive system

reproductive system phenotype ( J:165087 )

N • adult males show a normal number of Sertoli cells in the seminiferous tubules with no apparent defect in their position, cell volume or morphology

N • females are fully fertile

abnormal spermatogonia morphology ( J:165087 )

♂ • in adult testes, the number of undifferentiated spermatogonial cells is significantly reduced, as determined by TRA98 staining

♂ • however, the number of TRA98-positive cells at P5 is normal, indicating normal primordial germ cell (PGC) migration during embryogenesis

decreased male germ cell number ( J:165087 )

♂ • adult mice show a significant loss of TRA98-positive spermatogenic cells with no detectable changes in the numbers of PLZF-positive spermatogonial stem cells (SSCs)

♂ • adult testes show loss of c-Kit-positive type B spermatogonia and spermatocytes

increased testis apoptosis ( J:165087 )

♂ • at P10, TUNEL staining showed a 2.5-fold increase in apoptosis within the seminiferous tubules, whereas only a few TUNEL-positive cells are detected in wild-type testes

abnormal seminiferous tubule morphology ( J:165087 )

♂ • a paucity of cells is observed within seminiferous tubules

abnormal testis interstitial tissue morphology ( J:165087 )

♂ • focal hyperplasia of the testis interstitial components is observed

♂ • however, Leydig cell number is normal

small testis ( J:165087 )

♂ • males exhibit severe testicular hypotrophy at 24 weeks of age

decreased testis weight ( J:165087 )

♂ • average testis weight is significantly decreased at 24 weeks of age

abnormal spermatogenesis ( J:165087 )

♂ • spermatogenesis is severely impaired

azoospermia ( J:165087 )

♂ • decrease in number of spermatozoa ranges from oligozoospermia to azoospermia

oligozoospermia ( J:165087 )

♂ • number of spermatozoa obtained from the deferens ducts is significantly decreased

♂ • decrease in number of spermatozoa ranges from oligozoospermia to azoospermia

abnormal spermatogonia proliferation ( J:165087 )

♂ • number of actively proliferating PCNA and cyclin D1-positive cells is strikingly reduced at P10 and at 8 weeks of age

reduced male fertility ( J:165087 )

♂ • when males are mated with receptive females for 6 months, the number of litters produced per month is significantly lower than that for wild-type males

cellular

abnormal spermatogonia morphology ( J:165087 )

♂ • in adult testes, the number of undifferentiated spermatogonial cells is significantly reduced, as determined by TRA98 staining

♂ • however, the number of TRA98-positive cells at P5 is normal, indicating normal primordial germ cell (PGC) migration during embryogenesis

decreased male germ cell number ( J:165087 )

♂ • adult mice show a significant loss of TRA98-positive spermatogenic cells with no detectable changes in the numbers of PLZF-positive spermatogonial stem cells (SSCs)

♂ • adult testes show loss of c-Kit-positive type B spermatogonia and spermatocytes

azoospermia ( J:165087 )

♂ • decrease in number of spermatozoa ranges from oligozoospermia to azoospermia

oligozoospermia ( J:165087 )

♂ • number of spermatozoa obtained from the deferens ducts is significantly decreased

♂ • decrease in number of spermatozoa ranges from oligozoospermia to azoospermia

increased testis apoptosis ( J:165087 )

♂ • at P10, TUNEL staining showed a 2.5-fold increase in apoptosis within the seminiferous tubules, whereas only a few TUNEL-positive cells are detected in wild-type testes

abnormal spermatogonia proliferation ( J:165087 )

♂ • number of actively proliferating PCNA and cyclin D1-positive cells is strikingly reduced at P10 and at 8 weeks of age

homeostasis/metabolism

increased circulating follicle stimulating hormone level ( J:165087 )

♂ • adult males exhibit significantly higher plasma FSH levels than wild-type controls

♂ • in contrast, plasma testosterone levels are normal

endocrine/exocrine glands

increased testis apoptosis ( J:165087 )

♂ • at P10, TUNEL staining showed a 2.5-fold increase in apoptosis within the seminiferous tubules, whereas only a few TUNEL-positive cells are detected in wild-type testes

abnormal seminiferous tubule morphology ( J:165087 )

♂ • a paucity of cells is observed within seminiferous tubules

abnormal testis interstitial tissue morphology ( J:165087 )

♂ • focal hyperplasia of the testis interstitial components is observed

♂ • however, Leydig cell number is normal

small testis ( J:165087 )

♂ • males exhibit severe testicular hypotrophy at 24 weeks of age

decreased testis weight ( J:165087 )

♂ • average testis weight is significantly decreased at 24 weeks of age

Genotype
MGI:4358063

cx5

• Allelic Composition: Pik3cb^tm1.1Ehi/Pik3cb^tm1.1Ehi; Tg(MMTVneu)202Mul/0
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * BALB/c * C57BL/6J * FVB/N

neoplasm

decreased mammary gland tumor incidence ( J:152332 )

• development of first mammary tumor is delayed, number of tumors produced is decreased, and tumors growth is slower compared to in mice expression Tg(MMTVneu)202Mul alone

decreased tumor growth/size ( J:152332 )

• tumor growth is reduced compared to in mice expression Tg(MMTVneu)202Mul alone

integument

decreased mammary gland tumor incidence ( J:152332 )

• development of first mammary tumor is delayed, number of tumors produced is decreased, and tumors growth is slower compared to in mice expression Tg(MMTVneu)202Mul alone

endocrine/exocrine glands

decreased mammary gland tumor incidence ( J:152332 )

• development of first mammary tumor is delayed, number of tumors produced is decreased, and tumors growth is slower compared to in mice expression Tg(MMTVneu)202Mul alone