Phenotypes associated with this allele

• Allele Symbol: Esr1^tm1.2Mma
• Allele Name: targeted mutation 1.2, Manuel Mark
• Allele ID: MGI:3775510
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Esr1^tm1.2Mma/Esr1^tm1.2Mma Tg(Cga-cre)3Sac/0	involves: 129S2/SvPas * C57BL/6 * C57BL/6J * SJL	MGI:3798388
cn2	Esr1^tm1.2Mma/Esr1^tm1.2Mma Tg(Cyp17a1-icre)AJako/0	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:4361176
cn3	Esr1^tm1.2Mma/Esr1^tm1.2Mma Tg(Wnt7a-EGFP/cre)#Bhr/0	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:4887234

Genotype
MGI:3798388

cn1

• Allelic Composition: Esr1^tm1.2Mma/Esr1^tm1.2Mma; Tg(Cga-cre)3Sac/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/6J * SJL

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

reproductive system

ovarian follicular cyst ( J:131949 )

♀ • occasionally follicular cysts are observed in mice

abnormal estrous cycle ( J:131949 )

♀ • irregular cycling

female infertility ( J:131949 )

♀

endocrine/exocrine glands

ovarian follicular cyst ( J:131949 )

♀ • occasionally follicular cysts are observed in mice

growth/size/body

ovarian follicular cyst ( J:131949 )

♀ • occasionally follicular cysts are observed in mice

Genotype
MGI:4361176

cn2

• Allelic Composition: Esr1^tm1.2Mma/Esr1^tm1.2Mma; Tg(Cyp17a1-icre)AJako/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

cellular

oocyte degeneration ( J:151908 )

♀ • following induction of superovulation with PMSG and hCG, the majority of mutant oocytes exhibit signs of degeneration

mortality/aging

early reproductive senescence ( J:151908 )

• although mutant females display normal fertility and cycling at 2-3 months of age, they gradually lose fertility leading to near complete infertility by 6 months of age

reproductive system

ovary hemorrhage ( J:151908 )

♀ • at 4 months of age, mutant females display signs of hemorrhagic ovarian cysts; however, hemorrhagic cysts are significantly fewer than those observed in Esr1^tm1.1Mma females

♀ • following injection of PMSG alone or PMSG+hCG, mutant ovaries develop multiple hemorrhagic follicles, rarely observed in wild-type ovaries

oocyte degeneration ( J:151908 )

♀ • following induction of superovulation with PMSG and hCG, the majority of mutant oocytes exhibit signs of degeneration

abnormal ovary morphology ( J:151908 )

♀ • at 4 months of age, mutant ovaries display interstitial hypertrophy

decreased corpora lutea number ( J:151908 )

♀ • at 4 months of age, mutant females display reduced numbers of corpora lutea relative to age-matched control females

abnormal ovarian follicle number ( J:151908 )

♀ • at 4 months of age, mutant females exhibit increased numbers of late preantral and early antral stage follicles

abnormal theca cell layer morphology ( J:151908 )

♀ • following induction of superovulation with PMSG +hCG, most theca cells in mutant ovaries are abnormally located in interstitial areas, in contrast to wild-types ovaries where Cyp17-positive cells are mostly found in the theca interna of preovulatory follicles

increased theca cell number ( J:151908 )

♀ • following induction of superovulation with PMSG +hCG injections, ovaries of 6-month-old mutant females are more heavily populated with theca (Cyp17-positive) cells than wild-type ovaries

♀ • similarly, on the day of diestrus, ovaries of 4- and 10-month-old mutant females exhibit higher numbers of Cyp17-positive cells than wild-type ovaries

ovary cyst ( J:151908 )

♀ • at 4 months of age, unstimulated mutant females display signs of hemorrhagic ovarian cysts; however, hemorrhagic cysts are significantly fewer than those observed in Esr1^tm1.1Mma females

early reproductive senescence ( J:151908 )

• although mutant females display normal fertility and cycling at 2-3 months of age, they gradually lose fertility leading to near complete infertility by 6 months of age

decreased superovulation rate ( J:151908 )

♀ • following induction of superovulation with PMSG and hCG, significantly fewer numbers of oocytes are retrieved from the oviducts of 6-mo-old mutant females than from age-matched wild-type control females (6 vs 22 oocytes, respectively)

♀ • in contrast, only marginally smaller numbers of oocytes are retrieved at 2 months of age (20 vs 27 oocytes)

abnormal estrous cycle ( J:151908 )

♀ • at 4 months of age or later, all mutant females display an irregular pattern of estrous cycles relative to age-matched control littermates

prolonged diestrus ( J:151908 )

♀ • at 4- and 6 months of age, all mutant females exhibit a prolonged diestrous phase relative to age-matched control littermates

female infertility ( J:151908 )

♀ • female mutants become infertile before they reach 6 months of age

growth/size/body

ovary cyst ( J:151908 )

♀ • at 4 months of age, unstimulated mutant females display signs of hemorrhagic ovarian cysts; however, hemorrhagic cysts are significantly fewer than those observed in Esr1^tm1.1Mma females

endocrine/exocrine glands

ovary hemorrhage ( J:151908 )

♀ • at 4 months of age, mutant females display signs of hemorrhagic ovarian cysts; however, hemorrhagic cysts are significantly fewer than those observed in Esr1^tm1.1Mma females

♀ • following injection of PMSG alone or PMSG+hCG, mutant ovaries develop multiple hemorrhagic follicles, rarely observed in wild-type ovaries

increased gonadotroph cell number ( J:151908 )

• unexpectedly, at 4 months of age, mutant anterior pituitaries show a 2-fold increase in gonadotroph cell number relative to wild-type controls, with an approximately similar level of LH content in each cell

abnormal ovary morphology ( J:151908 )

♀ • at 4 months of age, mutant ovaries display interstitial hypertrophy

decreased corpora lutea number ( J:151908 )

♀ • at 4 months of age, mutant females display reduced numbers of corpora lutea relative to age-matched control females

abnormal ovarian follicle number ( J:151908 )

♀ • at 4 months of age, mutant females exhibit increased numbers of late preantral and early antral stage follicles

abnormal theca cell layer morphology ( J:151908 )

♀ • following induction of superovulation with PMSG +hCG, most theca cells in mutant ovaries are abnormally located in interstitial areas, in contrast to wild-types ovaries where Cyp17-positive cells are mostly found in the theca interna of preovulatory follicles

increased theca cell number ( J:151908 )

♀ • following induction of superovulation with PMSG +hCG injections, ovaries of 6-month-old mutant females are more heavily populated with theca (Cyp17-positive) cells than wild-type ovaries

♀ • similarly, on the day of diestrus, ovaries of 4- and 10-month-old mutant females exhibit higher numbers of Cyp17-positive cells than wild-type ovaries

ovary cyst ( J:151908 )

♀ • at 4 months of age, unstimulated mutant females display signs of hemorrhagic ovarian cysts; however, hemorrhagic cysts are significantly fewer than those observed in Esr1^tm1.1Mma females

homeostasis/metabolism

increased circulating testosterone level ( J:151908 )

• at 2- and 6-months of age, mutant females exhibit moderately increased basal levels of serum testosterone relative to wild-type control females

• in contrast, no significant differences in serum FSH or estradiol levels are observed

decreased circulating luteinizing hormone level ( J:151908 )

• in mutant females, serum LH levels are either markedly lower (2 months) or undetectable (6 months) relative to those in age-matched wild-type controls

nervous system

increased gonadotroph cell number ( J:151908 )

• unexpectedly, at 4 months of age, mutant anterior pituitaries show a 2-fold increase in gonadotroph cell number relative to wild-type controls, with an approximately similar level of LH content in each cell

cardiovascular system

ovary hemorrhage ( J:151908 )

♀ • at 4 months of age, mutant females display signs of hemorrhagic ovarian cysts; however, hemorrhagic cysts are significantly fewer than those observed in Esr1^tm1.1Mma females

♀ • following injection of PMSG alone or PMSG+hCG, mutant ovaries develop multiple hemorrhagic follicles, rarely observed in wild-type ovaries

Genotype
MGI:4887234

cn3

• Allelic Composition: Esr1^tm1.2Mma/Esr1^tm1.2Mma; Tg(Wnt7a-EGFP/cre)#Bhr/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

reproductive system

abnormal uterus morphology ( J:167551 )

♀ • in response to 17-beta-estradiol treatment, apoptosis in uterine glandular and luminal epithelium is significantly increased by 3 days post-treatment in mutants compared to treated wild-type

abnormal uterus size ( J:167551 )

♀ • in response to 17-beta-estradiol treatment, uterine weight increases in ovariectomized mutants but not as significantly as in ovariectomized wild-type females at 24 hours and 3 days after treatment

♀ • uterine proliferative response to ICI 182,780 (estrogen antagonist) is fully attenuated in wild-type and mutant females

abnormal uterine receptivity ( J:167551 )

♀ • in mutants, 0 of 6 implantation sites are observed following natural matings or embryo transfer in contrast to wild-type females where 6 of 9 implantation sites are detected