All Phenotypes Foxo3<tm1Rdp> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Foxo3^tm1Rdp
targeted mutation 1, Ronald DePinho
MGI:2668317

Summary

8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Foxo1^tm1Rdp/Foxo1^tm1Rdp Foxo3^tm1Rdp/Foxo3^tm1Rdp Tg(Mx1-cre)1Cgn/0	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * CBA * FVB/N	MGI:3706857
cn2	Foxo1^tm1Rdp/Foxo1^tm1.1Rdp Foxo3^tm1Rdp/Foxo3^tm1.1Rdp Pten^tm1Hwu/Pten^tm1Hwu Tg(CYP19A1-cre)1Jri/0	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:5784501
cn3	Foxo1^tm1Rdp/Foxo1^tm1.1Rdp Foxo3^tm1Rdp/Foxo3^tm1.1Rdp Tg(CYP19A1-cre)1Jri/0	involves: 129S6/SvEvTac	MGI:5784494
cn4	Foxo1^tm1Rdp/Foxo1^tm1.1Rdp Foxo3^tm1Rdp/Foxo3^tm1.1Rdp Amhr2^tm3(cre)Bhr/Amhr2⁺	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:5784489
cn5	Foxo1^tm1Rdp/Foxo1^tm1Rdp Foxo3^tm1Rdp/Foxo3^tm1Rdp Foxo4^tm1Rdp/Foxo4^tm1Rdp Tg(Ins2-cre)23Herr/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * CBA/J	MGI:5638417
cn6	Foxo1^tm1Rdp/Foxo1^tm1Rdp Foxo3^tm1Rdp/Foxo3^tm1Rdp Foxo4^tm1Rdp/Foxo4^tm1Rdp Tg(Mx1-cre)1Cgn/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N	MGI:3706822
cn7	Foxo3^tm1Rdp/Foxo3^tm1Rdp Tg(Ddx4-cre/ERT2)1Dcas/0	involves: 129S6/SvEvTac * FVB/N	MGI:4882149
cn8	Foxo3^tm1Rdp/Foxo3^tm1Rdp Tg(Ddx4-cre)1Dcas/0	involves: 129S6/SvEvTac * FVB/N	MGI:4882147

Allelic Composition	Foxo1^tm1Rdp/Foxo1^tm1Rdp Foxo3^tm1Rdp/Foxo3^tm1Rdp Tg(Mx1-cre)1Cgn/0
Genetic Background	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6 * CBA * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo1^tm1Rdp mutation (2 available); any Foxo1 mutation (32 available)
Foxo3^tm1Rdp mutation (1 available); any Foxo3 mutation (51 available)
Tg(Mx1-cre)1Cgn mutation (7 available)

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

mortality/aging

premature death ( J:118179 )

• development of hemangiomas leads to premature death starting at ~55 weeks of age with induced cre expression

neoplasm

increased tumor incidence ( J:118179 )

increased hemangioma incidence ( J:118179 )

• mice show widespread development of hemangiomas after cre induction; lesions are most exaggerated in uterus, visible at 6-8 weeks

increased hepatic hemangioma incidence ( J:118179 )

• discrete liver hemangiomas and occasionally angiosarcomas are observed in aged mice (7/10 that died at 50-82 weeks and 2/2 examined at 90-102 weeks)

increased hemangiosarcoma incidence ( J:118179 )

• in ~9% of mice, lesions progress to lethal angiosarcomas

cardiovascular system

abnormal blood vessel morphology ( J:118179 )

• all mice display mild vascular abnormalities with cre expression

liver/biliary system

increased hepatic hemangioma incidence ( J:118179 )

• discrete liver hemangiomas and occasionally angiosarcomas are observed in aged mice (7/10 that died at 50-82 weeks and 2/2 examined at 90-102 weeks)

Allelic Composition	Foxo1^tm1Rdp/Foxo1^tm1.1Rdp Foxo3^tm1Rdp/Foxo3^tm1.1Rdp Pten^tm1Hwu/Pten^tm1Hwu Tg(CYP19A1-cre)1Jri/0
Genetic Background	involves: 129S4/SvJae * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo1^tm1.1Rdp mutation (0 available); any Foxo1 mutation (32 available)
Foxo1^tm1Rdp mutation (2 available); any Foxo1 mutation (32 available)
Foxo3^tm1.1Rdp mutation (1 available); any Foxo3 mutation (51 available)
Foxo3^tm1Rdp mutation (1 available); any Foxo3 mutation (51 available)
Pten^tm1Hwu mutation (16 available); any Pten mutation (88 available)
Tg(CYP19A1-cre)1Jri mutation (1 available)

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

endocrine/exocrine glands

increased granulosa cell tumor incidence ( J:232961 )

• 60% incidence of granulosa cell tumor occurrence, with early tumor development

• granulosa cell tumors are either solid and surrounded by a thin layer of ovarian tissue containing a few growing follicles or are larger and contain tubular-like structures of different sizes and shapes surrounded by a basal lamina of collagen IV

• mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early

homeostasis/metabolism

abnormal circulating hormone level ( J:232961 )

• tumor bearing mice exhibit increased levels of serum inhibin A and inhibin B

suppressed circulating follicle stimulating hormone level ( J:232961 )

• serum follicle stimulating hormone levels are below the level of detection in tumor bearing mice

decreased circulating luteinizing hormone level ( J:232961 )

• serum luteinizing hormone levels are below the level of detection in tumor bearing mice

neoplasm

increased granulosa cell tumor incidence ( J:232961 )

• 60% incidence of granulosa cell tumor occurrence, with early tumor development

• mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early

reproductive system

increased granulosa cell tumor incidence ( J:232961 )

• 60% incidence of granulosa cell tumor occurrence, with early tumor development

• mice injected with superovulatory levels of equine gonadotropin and human gonadotropin at 6 weeks of age develop large granulosa cell tumors early

Allelic Composition	Foxo1^tm1Rdp/Foxo1^tm1.1Rdp Foxo3^tm1Rdp/Foxo3^tm1.1Rdp Tg(CYP19A1-cre)1Jri/0
Genetic Background	involves: 129S6/SvEvTac

Find Mice

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

endocrine/exocrine glands

abnormal ovarian follicle morphology ( J:232961 )

• 1.5 month old mice injected with superovulatory levels of equine gonadotropin and human gonadotropin exhibit ovaries with many abnormal, degenerating follicles in which oocytes are shrunken or absent

abnormal granulosa cell morphology ( J:232961 )

• in some ovarian follicles of mice injected with superovulatory levels of equine gonadotropin and human gonadotropin, granulosa cells are abnormally displaced and growing on one side

increased granulosa cell tumor incidence ( J:232961 )

• about 20% of mice develop granulosa cell tumors by 6-8 months of age

• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures

• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis

• 65% of 1.5 month old mice injected with superovulatory levels of equine gonadotropin and human gonadotropin develop granulosa cell tumors or cysts

homeostasis/metabolism

abnormal circulating hormone level ( J:232961 )

• tumor bearing mice exhibit increased levels of serum inhibin A and inhibin B

increased circulating estradiol level ( J:232961 )

• serum levels of estradiol are elevated in tumor bearing mice

suppressed circulating follicle stimulating hormone level ( J:232961 )

• serum follicle stimulating hormone levels are below the level of detection in tumor bearing mice

decreased circulating luteinizing hormone level ( J:232961 )

• serum luteinizing hormone levels are below the level of detection in tumor bearing mice

neoplasm

increased granulosa cell tumor incidence ( J:232961 )

• about 20% of mice develop granulosa cell tumors by 6-8 months of age

• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures

• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis

• 65% of 1.5 month old mice injected with superovulatory levels of equine gonadotropin and human gonadotropin develop granulosa cell tumors or cysts

reproductive system

abnormal ovarian follicle morphology ( J:232961 )

abnormal granulosa cell morphology ( J:232961 )

• in some ovarian follicles of mice injected with superovulatory levels of equine gonadotropin and human gonadotropin, granulosa cells are abnormally displaced and growing on one side

increased granulosa cell tumor incidence ( J:232961 )

• about 20% of mice develop granulosa cell tumors by 6-8 months of age

• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures

• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis

• 65% of 1.5 month old mice injected with superovulatory levels of equine gonadotropin and human gonadotropin develop granulosa cell tumors or cysts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:232961

Allelic Composition	Foxo1^tm1Rdp/Foxo1^tm1.1Rdp Foxo3^tm1Rdp/Foxo3^tm1.1Rdp Amhr2^tm3(cre)Bhr/Amhr2⁺
Genetic Background	involves: 129S6/SvEvTac * 129S7/SvEvBrd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Amhr2^tm3(cre)Bhr mutation (1 available); any Amhr2 mutation (29 available)
Foxo1^tm1.1Rdp mutation (0 available); any Foxo1 mutation (32 available)
Foxo1^tm1Rdp mutation (2 available); any Foxo1 mutation (32 available)
Foxo3^tm1.1Rdp mutation (1 available); any Foxo3 mutation (51 available)
Foxo3^tm1Rdp mutation (1 available); any Foxo3 mutation (51 available)

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

endocrine/exocrine glands

abnormal ovarian follicle morphology ( J:232961 )

• ovaries of 3-4 month old mice contain many small abnormal follicles in which fragmented oocytes or only remnants of the zona pellucida are evident

• some follicles in 3-4 month old mice assume the appearance of testicular-like structures

increased granulosa cell tumor incidence ( J:232961 )

• about 20% of mice develop granulosa cell tumors by 6-8 months of age

• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures

• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis

ovary cyst ( J:232961 )

• ovaries of 3-4 month old mice typically contain large cyst-like structures, some of which are hemorrhagic

homeostasis/metabolism

abnormal circulating hormone level ( J:232961 )

• tumor bearing mice exhibit increased levels of serum inhibin A and inhibin B

increased circulating estradiol level ( J:232961 )

• serum levels of estradiol are elevated in tumor bearing mice

suppressed circulating follicle stimulating hormone level ( J:232961 )

• serum follicle stimulating hormone levels are below the level of detection in tumor bearing mice

decreased circulating luteinizing hormone level ( J:232961 )

• serum luteinizing hormone levels are below the level of detection in tumor bearing mice

neoplasm

increased granulosa cell tumor incidence ( J:232961 )

• about 20% of mice develop granulosa cell tumors by 6-8 months of age

• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures

• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis

reproductive system

abnormal ovarian follicle morphology ( J:232961 )

• ovaries of 3-4 month old mice contain many small abnormal follicles in which fragmented oocytes or only remnants of the zona pellucida are evident

• some follicles in 3-4 month old mice assume the appearance of testicular-like structures

increased granulosa cell tumor incidence ( J:232961 )

• about 20% of mice develop granulosa cell tumors by 6-8 months of age

• most tumors from 6-11 months of age are unilateral and solid with regions of trabecular- and gyriform-like structures

• some tumors contain cystic or hemorrhagic follicle-like structures devoid of oocytes and/or regions of necrosis

ovary cyst ( J:232961 )

• ovaries of 3-4 month old mice typically contain large cyst-like structures, some of which are hemorrhagic

growth/size/body

ovary cyst ( J:232961 )

• ovaries of 3-4 month old mice typically contain large cyst-like structures, some of which are hemorrhagic

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:232961

Allelic Composition	Foxo1^tm1Rdp/Foxo1^tm1Rdp Foxo3^tm1Rdp/Foxo3^tm1Rdp Foxo4^tm1Rdp/Foxo4^tm1Rdp Tg(Ins2-cre)23Herr/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * CBA/J

Find Mice

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

homeostasis/metabolism

abnormal glucose homeostasis ( J:215526 )

• mice show a defect in glucose-dependent insulin secretion that leads to early-onset, mild and moderately progressive diabetes

• mice subjected to hyperglycemic clamps require an approximate 50% lower rate of glucose infusion to maintain steady-state hyperglycemia

decreased insulin secretion ( J:215526 )

• mice are impaired in secreting insulin in response to the ATP-dependent K-channel blocker, glibenclamide, and to the depolarizing agent, I-arginine

• beta cells exhibit reduced calcium-dependent insulin secretion

• purified islets show lower insulin secretion in response to the sulfonylurea glibenclamide, the PKC activator PMA, and the L-type Ca channel activator Bay-K8644

hyperglycemia ( J:215526 )

• mice exhibit hyperglycemia in the fasted, refed, and random-fed states as early as 12 weeks of age

decreased circulating insulin level ( J:215526 )

• mice exhibit lower plasma insulin levels in fasted, refed, and random-fed states, although not significant in the latter state

impaired glucose tolerance ( J:215526 )

• mice show impaired glucose tolerance that worsens progressively with age during intraperitoneal glucose tolerance tests, without changes to peripheral insulin sensitivity

endocrine/exocrine glands

abnormal pancreatic beta cell differentiation ( J:215526 )

• as mice age to 12 months, beta cell dedifferentiation occurs

abnormal pancreatic beta cell physiology ( J:215526 )

• beta cells are metabolically inflexible such that they preferentially utilize lipids rather than carbohydrates as an energy source resulting in impaired ATP generation and reduced calcium-dependent insulin secretion

• glucose oxidation to carbon dioxide is impaired by about 50% in islets at most glucose concentrations

• palmitate oxidation by islets in the presence of basal glucose is 2-fold higher and nearly 2.5-fold higher in high glucose

• glycerolipid synthesis of islets is normal at low glucose concentrations but fails to increase at elevated glucose concentrations, resulting in lower conversion of palmitate into diacylglycerides and triglycerides indicating that beta cells appear to be locked in a lipid oxidative state

• membrane depolarization-induced calcium influx in response to rising glucose concentrations is lower in beta cells

decreased insulin secretion ( J:215526 )

• mice are impaired in secreting insulin in response to the ATP-dependent K-channel blocker, glibenclamide, and to the depolarizing agent, I-arginine

• beta cells exhibit reduced calcium-dependent insulin secretion

• purified islets show lower insulin secretion in response to the sulfonylurea glibenclamide, the PKC activator PMA, and the L-type Ca channel activator Bay-K8644

cellular

abnormal pancreatic beta cell differentiation ( J:215526 )

• as mice age to 12 months, beta cell dedifferentiation occurs

abnormal mitochondrial physiology ( J:215526 )

• islets show a decrease in glucose-induced oxygen consumption

• raising glucose levels does not increase ATP turnover in purified islets as in control islets

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young		DOID:0050524	OMIM:606391	J:215526

Allelic Composition	Foxo1^tm1Rdp/Foxo1^tm1Rdp Foxo3^tm1Rdp/Foxo3^tm1Rdp Foxo4^tm1Rdp/Foxo4^tm1Rdp Tg(Mx1-cre)1Cgn/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N

Find Mice

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

mortality/aging

premature death ( J:118179 )

• induced mice start to show significant mortality starting at ~22 weeks with ~90% mortality by 75 weeks of age

neoplasm

increased T cell derived lymphoma incidence ( J:118179 )

• by 19-30 weeks, after cre induction, mice develop aggressive CD8+ CD4+ thymic lymphomas that spread to the spleen, lymph nodes and liver

• wild-type mice and all other conditional genotypes examined here do not show any lymphomas up to 100 weeks of age

increased hamartoma incidence ( J:118179 )

• mice develop an age-progressive hamarotomatous phenotype with cre expression

increased hemangioma incidence ( J:118179 )

• mice show widespread development of hemangiomas, most exaggerated in uterus and visible by 6-8 weeks

• lesions (usually benign) progress greatly by 30-40 weeks, with affected animals showing massive hemangiomas with intraluminal blood and thrombi in skeletal muscle, abdominal wall, liver, adrenal glands, bone marrow, omentum, lymph nodes, and skin

increased hemangiosarcoma incidence ( J:118179 )

• in ~9% of mice, lesions progress to lethal angiosarcomas

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:118179 )

• by 19-30 weeks, after cre induction, mice develop aggressive CD8+ CD4+ thymic lymphomas that spread to the spleen, lymph nodes and liver

• wild-type mice and all other conditional genotypes examined here do not show any lymphomas up to 100 weeks of age

hematopoietic system

increased T cell derived lymphoma incidence ( J:118179 )

• by 19-30 weeks, after cre induction, mice develop aggressive CD8+ CD4+ thymic lymphomas that spread to the spleen, lymph nodes and liver

• wild-type mice and all other conditional genotypes examined here do not show any lymphomas up to 100 weeks of age

immune system

increased T cell derived lymphoma incidence ( J:118179 )

• by 19-30 weeks, after cre induction, mice develop aggressive CD8+ CD4+ thymic lymphomas that spread to the spleen, lymph nodes and liver

• wild-type mice and all other conditional genotypes examined here do not show any lymphomas up to 100 weeks of age

Allelic Composition	Foxo3^tm1Rdp/Foxo3^tm1Rdp Tg(Ddx4-cre/ERT2)1Dcas/0
Genetic Background	involves: 129S6/SvEvTac * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo3^tm1Rdp mutation (1 available); any Foxo3 mutation (51 available)
Tg(Ddx4-cre/ERT2)1Dcas mutation (1 available)

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

endocrine/exocrine glands

abnormal primordial ovarian follicle morphology ( J:138697 )

• mutants treated with tamoxifen to induce cre expression exhibit global follicle activation

enlarged ovary ( J:138697 )

• mutants treated with tamoxifen to induce cre expression exhibit ovarian hypertrophy

reproductive system

abnormal primordial ovarian follicle morphology ( J:138697 )

• mutants treated with tamoxifen to induce cre expression exhibit global follicle activation

enlarged ovary ( J:138697 )

• mutants treated with tamoxifen to induce cre expression exhibit ovarian hypertrophy

growth/size/body

enlarged ovary ( J:138697 )

• mutants treated with tamoxifen to induce cre expression exhibit ovarian hypertrophy

Allelic Composition	Foxo3^tm1Rdp/Foxo3^tm1Rdp Tg(Ddx4-cre)1Dcas/0
Genetic Background	involves: 129S6/SvEvTac * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo3^tm1Rdp mutation (1 available); any Foxo3 mutation (51 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)

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

endocrine/exocrine glands

abnormal primordial ovarian follicle morphology ( J:138697 )

• global primordial follicle activation

enlarged ovary ( J:138697 )

abnormal ovary physiology ( J:138697 )

• ovaries explanted at birth and cultured for 8 days grow more rapidly than controls

reproductive system

abnormal primordial ovarian follicle morphology ( J:138697 )

• global primordial follicle activation

enlarged ovary ( J:138697 )

abnormal ovary physiology ( J:138697 )

• ovaries explanted at birth and cultured for 8 days grow more rapidly than controls

growth/size/body

enlarged ovary ( J:138697 )

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