Phenotypes associated with this allele

• Allele Symbol: Foxo3^tm1.1Rdp
• Allele Name: targeted mutation 1.1, Ronald DePinho
• Allele ID: MGI:2668328
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxo3^tm1.1Rdp/Foxo3^tm1.1Rdp	involves: 129S6/SvEvTac * FVB/N	MGI:2668335
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
cx5	Foxo3^tm1.1Rdp/Foxo3^+ Foxo4^tm1.1Rdp/Foxo4^tm1.1Rdp	involves: 129S1/Sv * 129S6/SvEvTac * FVB/N	MGI:3706828
cx6	Foxo3^tm1.1Rdp/Foxo3^tm1.1Rdp Foxo4^tm1.1Rdp/Foxo4^tm1.1Rdp	involves: 129S1/Sv * 129S6/SvEvTac * FVB/N	MGI:3706813
cx7	Foxo3^mommeR1/Foxo3^tm1.1Rdp Tg(HBA1-GFP)1Ew/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/NJ	MGI:4949206

Genotype
MGI:2668335

hm1

• Allelic Composition: Foxo3^tm1.1Rdp/Foxo3^tm1.1Rdp
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

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

cellular

abnormal oocyte morphology ( J:84269 )

♀ • oocytes were observed to be enlarged and misshapen, first evident at 8 days of age

mortality/aging

premature death ( J:118179 )

• mutants with dermatitis survive ~90-95 weeks, while those that remain dermatitis-free survive ~110 weeks compared to heterozygotes or wild-type which can survive past 140 weeks

early reproductive senescence ( J:84269 , J:118179 )

• females were sterile by 15 weeks of age (J:84269)

• female develop premature sterility due to global activation of primordial follicles soon after birth (J:118179)

neoplasm

increased prolactinoma incidence ( J:118179 )

• female mice show shorter latency and increased growth of pituitary prolactinomas (7/16 vs 1/10 wild-type)

increased ovary tumor incidence ( J:118179 )

♀ • females show an increased incidence of ovarian neoplasms (4/16 compared to 0/10 wild-type)

increased hemangiosarcoma incidence ( J:118179 )

• after carcinogen (DMBA) treatment, homozygotes and heterozygotes show increased incidence of angiosarcomas compared to wild-type

decreased tumor latency ( J:118179 )

• 19/20 dermatitis-free mice develop tumors more rapidly (starting at ~25) and show a more rapid onset of tumors compared to mice developing dermatitis (tumors develop at ~90-95 weeks)

growth/size/body

enlarged ovary ( J:84269 )

♀ • enlarged ovaries evident by 8 to 14 days of age

nervous system

increased prolactinoma incidence ( J:118179 )

• female mice show shorter latency and increased growth of pituitary prolactinomas (7/16 vs 1/10 wild-type)

reproductive system

abnormal oocyte morphology ( J:84269 )

♀ • oocytes were observed to be enlarged and misshapen, first evident at 8 days of age

increased atretic ovarian follicle number ( J:84269 )

♀ • increased atresia by 8.5 weeks of age

abnormal ovarian folliculogenesis ( J:84269 )

♀ • increased activation resulting in the progression of increased numbers of follicles to more advanced stages of follicular development

♀ • increased atresia by 8.5 weeks of age

enlarged ovary ( J:84269 )

♀ • enlarged ovaries evident by 8 to 14 days of age

increased ovary tumor incidence ( J:118179 )

♀ • females show an increased incidence of ovarian neoplasms (4/16 compared to 0/10 wild-type)

early reproductive senescence ( J:84269 , J:118179 )

• females were sterile by 15 weeks of age (J:84269)

• female develop premature sterility due to global activation of primordial follicles soon after birth (J:118179)

abnormal estrous cycle ( J:84269 )

♀ • females cycled sporadically from 6 to 15 weeks but became acyclic

absent estrous cycle ( J:84269 )

♀ • females became acyclic after 15 weeks of age

reduced female fertility ( J:84269 )

♀ • age dependent decline in female reproductive ability

immune system

dermatitis ( J:118179 )

• mice develop dermatitis between 10-24 months of age; 15/35 mice had to be euthanized due to progressive skin ulcerations

hematopoietic system

anemia ( J:84269 )

• mild compensated anemia

hemolytic anemia ( J:118179 )

• mice develop mild hemolytic anemia

reticulocytosis ( J:84269 )

homeostasis/metabolism

increased circulating follicle stimulating hormone level ( J:84269 )

increased circulating luteinizing hormone level ( J:84269 )

impaired glucose tolerance ( J:84269 , J:118179 )

• decreased rate of glucose uptake following fast (J:84269)

• modest glucose intolerance is observed (J:118179)

endocrine/exocrine glands

increased prolactinoma incidence ( J:118179 )

• female mice show shorter latency and increased growth of pituitary prolactinomas (7/16 vs 1/10 wild-type)

increased atretic ovarian follicle number ( J:84269 )

♀ • increased atresia by 8.5 weeks of age

abnormal ovarian folliculogenesis ( J:84269 )

♀ • increased activation resulting in the progression of increased numbers of follicles to more advanced stages of follicular development

♀ • increased atresia by 8.5 weeks of age

enlarged ovary ( J:84269 )

♀ • enlarged ovaries evident by 8 to 14 days of age

increased ovary tumor incidence ( J:118179 )

♀ • females show an increased incidence of ovarian neoplasms (4/16 compared to 0/10 wild-type)

integument

dermatitis ( J:118179 )

• mice develop dermatitis between 10-24 months of age; 15/35 mice had to be euthanized due to progressive skin ulcerations

Genotype
MGI:5784501

cn2

• 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

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

♀ • 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

reproductive system

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

Genotype
MGI:5784494

cn3

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

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 )

♀ • 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

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

Genotype
MGI:5784489

cn4

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

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

Genotype
MGI:3706828

cx5

• Allelic Composition: Foxo3^tm1.1Rdp/Foxo3⁺; Foxo4^tm1.1Rdp/Foxo4^tm1.1Rdp
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * FVB/N

neoplasm

increased tumor incidence ( J:118179 )

♀ • other unclassified tumors are seen with higher frequencies (1/9 vs 0 wild-type)

increased pituitary adenoma incidence ( J:118179 )

♀ • females show increased pituitary adenoma (1/5 vs 0 wild-type)

increased Harderian gland tumor incidence ( J:118179 )

♀ • mice show increased incidence of Harderian gland tumors (2/9 vs 1/6 wild-type)

increased ovary tumor incidence ( J:118179 )

♀ • slightly increased incidence of ovarian stromal neoplasms in females (1/5 vs 0 wild-type)

reproductive system

increased ovary tumor incidence ( J:118179 )

♀ • slightly increased incidence of ovarian stromal neoplasms in females (1/5 vs 0 wild-type)

endocrine/exocrine glands

increased pituitary adenoma incidence ( J:118179 )

♀ • females show increased pituitary adenoma (1/5 vs 0 wild-type)

increased Harderian gland tumor incidence ( J:118179 )

♀ • mice show increased incidence of Harderian gland tumors (2/9 vs 1/6 wild-type)

increased ovary tumor incidence ( J:118179 )

♀ • slightly increased incidence of ovarian stromal neoplasms in females (1/5 vs 0 wild-type)

nervous system

increased pituitary adenoma incidence ( J:118179 )

♀ • females show increased pituitary adenoma (1/5 vs 0 wild-type)

Genotype
MGI:3706813

cx6

• Allelic Composition: Foxo3^tm1.1Rdp/Foxo3^tm1.1Rdp; Foxo4^tm1.1Rdp/Foxo4^tm1.1Rdp
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * FVB/N

neoplasm

increased tumor incidence ( J:118179 )

♀ • other unclassified tumors are seen with higher frequencies (3/27 vs 0 wild-type)

increased pituitary adenoma incidence ( J:118179 )

♀ • females show increased pituitary adenoma (6/13 vs 0 wild-type)

increased Harderian gland tumor incidence ( J:118179 )

♀ • mice show increased incidence of Harderian gland tumors (4/27 vs 1/6 wild-type)

increased ovary tumor incidence ( J:118179 )

♀ • slightly increased incidence of ovarian stromal neoplasms (1/13 vs o wild-type)

increased ovarian teratoma incidence ( J:118179 )

♀ • increased incidence of cystic teratoma (ovary) compared to wild-type (2/13 vs 0 wild-type)

increased lung adenoma incidence ( J:118179 )

♀ • increased incidence of lung tumors (7/27 mice vs 1/6 wild-type)

respiratory system

increased lung adenoma incidence ( J:118179 )

♀ • increased incidence of lung tumors (7/27 mice vs 1/6 wild-type)

reproductive system

increased ovary tumor incidence ( J:118179 )

♀ • slightly increased incidence of ovarian stromal neoplasms (1/13 vs o wild-type)

increased ovarian teratoma incidence ( J:118179 )

♀ • increased incidence of cystic teratoma (ovary) compared to wild-type (2/13 vs 0 wild-type)

nervous system

increased pituitary adenoma incidence ( J:118179 )

♀ • females show increased pituitary adenoma (6/13 vs 0 wild-type)

endocrine/exocrine glands

increased pituitary adenoma incidence ( J:118179 )

♀ • females show increased pituitary adenoma (6/13 vs 0 wild-type)

increased Harderian gland tumor incidence ( J:118179 )

♀ • mice show increased incidence of Harderian gland tumors (4/27 vs 1/6 wild-type)

increased ovary tumor incidence ( J:118179 )

♀ • slightly increased incidence of ovarian stromal neoplasms (1/13 vs o wild-type)

increased ovarian teratoma incidence ( J:118179 )

♀ • increased incidence of cystic teratoma (ovary) compared to wild-type (2/13 vs 0 wild-type)

Genotype
MGI:4949206

cx7

• Allelic Composition: Foxo3^mommeR1/Foxo3^tm1.1Rdp; Tg(HBA1-GFP)1Ew/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/NJ

reproductive system

decreased primary ovarian follicle number ( J:170710 )

♀ • marked reduction in the number of primary follicles in some mice at 12 weeks of age

decreased primordial ovarian follicle number ( J:170710 )

♀ • marked reduction in the number of primordial follicles in some mice at 12 weeks of age

absent ovarian follicles ( J:170710 )

♀ • in some mice at 12 weeks of age

neoplasm

neoplasm ( J:170710 )

N • unlike mice homozygous for Foxo3^mommeR1 no ovarian teratomas are detected (in 7 mice)

endocrine/exocrine glands

decreased primary ovarian follicle number ( J:170710 )

♀ • marked reduction in the number of primary follicles in some mice at 12 weeks of age

decreased primordial ovarian follicle number ( J:170710 )

♀ • marked reduction in the number of primordial follicles in some mice at 12 weeks of age

absent ovarian follicles ( J:170710 )

♀ • in some mice at 12 weeks of age