Phenotypes associated with this allele

• Allele Symbol: Pgr^tm2(cre)Lyd
• Allele Name: targeted mutation 2, John P Lydon
• Allele ID: MGI:3576366
• Summary: 38 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * C57BL/6	MGI:3813634
cn2	Lepr^tm1.1Chua/Lepr^tm1.1Chua Pgr^tm2(cre)Lyd/Pgr^+	involves: 129 * C57BL/6J * FVB/NJ	MGI:7278688
cn3	Pgr^tm2(cre)Lyd/Pgr^+ Rbpj^tm1Hon/Rbpj^tm1Hon	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:7333164
cn4	Men1^tm1.2Zqw/Men1^tm1.2Zqw Pgr^tm2(cre)Lyd/Pgr^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7434127
cn5	Foxa2^tm1Khk/Foxa2^tm1Khk Pgr^tm2(cre)Lyd/Pgr^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6854709
cn6	Pgr^tm2(cre)Lyd/Pgr^+ Trp53^tm1Brn/Trp53^tm1Brn	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3813635
cn7	Apc^tm1Rsmi/Apc^tm1Rsmi Pgr^tm2(cre)Lyd/Pgr^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5583019
cn8	Wnt11^tm1.1Khay/Wnt11^tm1.2Khay Pgr^tm2(cre)Lyd/Pgr^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:4946386
cn9	Wnt7a^tm1.1Tesp/Wnt7a^tm1.1Tesp Pgr^tm2(cre)Lyd/Pgr^+	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * SJL	MGI:5285205
cn10	Ncoa2^tm1.1Ipc/Ncoa2^tm1.1Ipc Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3716551
cn11	Errfi1^tm1Jwj/Errfi1^tm1Jwj Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4944273
cn12	Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4944272
cn13	Pgr^tm2(cre)Lyd/Pgr^+ Ror1^tm1.1Meg/Ror1^tm1.1Meg Ror2^tm1.1Meg/Ror2^tm1.1Meg	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:5901907
cn14	Gt(ROSA)26Sor^tm1(CAG-Errfi1)Jwj/? Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:5780554
cn15	Pgr^tm2(cre)Lyd/Pgr^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:3813633
cn16	Gt(ROSA)26Sor^tm1(CAG-NR2F1)Mjts/Gt(ROSA)26Sor^+ Nr2f2^tm2.1Tsa/Nr2f2^tm2.1Tsa Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:5474794
cn17	Nr2f2^tm2.1Tsa/Nr2f2^tm2.1Tsa Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:5474795
cn18	Pgr^tm2(cre)Lyd/Pgr^+ Wnt5a^tm1.1Tpy/Wnt5a^tm1.1Tpy	involves: 129S1/Sv * 129X1/SvJ	MGI:5901913
cn19	Gt(ROSA)26Sor^tm2(CAG-Nr5a1)Fjd/Gt(ROSA)26Sor^+ Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ	MGI:6275549
cn20	Tsc2^tm1.1Mjg/Tsc2^tm1.1Mjg Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5641710
cn21	Klf5^tm1Jaw/Klf5^tm1Jaw Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ	MGI:6870538
cn22	Gata2^tm1Sac/Gata2^tm1Sac Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ	MGI:7264294
cn23	Phb2^tm2.1Katz/Phb2^tm2.1Katz Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5299193
cn24	Phb2^tm2.1Katz/Phb2^+ Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5299191
cn25	Errfi1^tm1Jwj/Errfi1^tm1Jwj Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3850221
cn26	Ezh2^tm2Sho/Ezh2^tm2Sho Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6827353
cn27	Gt(ROSA)26Sor^tm1(CAG-Wnt5a,-AcGFP)Skde/Gt(ROSA)26Sor^+ Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5901730
cn28	Gt(ROSA)26Sor^tm1(CAG-Errfi1)Jwj/? Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5780553
cn29	Pgrmc1^tm1.1Jjp/Pgrmc1^tm1.1Jjp Pgrmc2^tm1.1Jjp/Pgrmc2^+ Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6118935
cn30	Pgrmc1^tm1.1Jjp/Pgrmc1^tm1.1Jjp Pgrmc2^tm1.1Jjp/Pgrmc2^tm1.1Jjp Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6118934
cn31	Pgrmc2^tm1.1Jjp/Pgrmc2^+ Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6118933
cn32	Pgrmc2^tm1.1Jjp/Pgrmc2^tm1.1Jjp Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6118932
cn33	Atg16l1^tm1c(EUCOMM)Wtsi/Atg16l1^tm1c(EUCOMM)Wtsi Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6N	MGI:6850681
cn34	Phb1^tm1.1Bwo/Phb1^tm1.1Bwo Pgr^tm2(cre)Lyd/?	involves: 129S7/SvEvBrd * C57BL/6	MGI:5052044
cn35	Hdac3^tm1.1Eno/Hdac3^tm1.1Eno Pgr^tm2(cre)Lyd/Pgr^+	involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6281662
cn36	Ncoa1^tm1Bwo/Ncoa1^tm1Bwo Ncoa2^tm1.1Ipc/Ncoa2^tm1.1Ipc Pgr^tm2(cre)Lyd/Pgr^+	involves: 129/Sv * 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3716555
cn37	Pgr^tm2(cre)Lyd/Pgr^+ Cripto^tm2.2Mms/Cripto^tm2.2Mms	involves: 129/Sv * C57BL/6N * CD-1	MGI:7279155
cn38	Ncoa6^tm3Jxu/Ncoa6^tm3Jxu Pgr^tm2(cre)Lyd/Pgr^+	involves: 129/Sv * C57BL/6 * SJL	MGI:5444650

Genotype
MGI:3813634

cn1

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * C57BL/6

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

mortality/aging

premature death ( J:139053 )

• impaired survival is seen beginning around 2 months of age

• death appears to result from excessive bleeding due to invasion of uterine blood vessels by tumor cells

reproductive system

increased endometrial carcinoma incidence ( J:139053 )

♀ • hyperplasia progresses to carcinoma by 3 weeks of age

endometrium hyperplasia ( J:139053 )

♀ • by P10, luminal and glandular epithelial hyperplasia are seen

enlarged uterus ( J:139053 )

♀ • enlarged relative to conditional mutants that are wild type for Trp53

neoplasm

increased endometrial carcinoma incidence ( J:139053 )

♀ • hyperplasia progresses to carcinoma by 3 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometrial cancer		DOID:1380	OMIM:608089	J:139053

Genotype
MGI:7278688

cn2

• Allelic Composition: Lepr^tm1.1Chua/Lepr^tm1.1Chua; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129 * C57BL/6J * FVB/NJ

reproductive system

reproductive system phenotype ( J:324160 )

♀N • virgin females exhibited normal estrous cycle length in days relative to control females

abnormal embryo implantation ( J:324160 )

♀ • at day 6.5 of pregnancy, the ratio of viable implantation sites to corpora lutea was significantly lower than in controls, suggesting reduced implantation efficiency

♀ • however, no significant differences are observed in the average number of implantation sites or corpora lutea at day 6.5 of pregnancy

abnormal parturition ( J:324160 )

♀ • dams exhibited a high incidence of stillbirth and dystocia, indicating labor dysfunction

♀ • however, pregnancy was normal at day 17.5, as determined by maternal weight, fetal weight, number of live fetuses, number of resorption sites, and placental weight and structure

delayed parturition ( J:324160 )

♀ • with increasing parity, dams took increasingly longer than controls to produce pups after being placed with a proven breeder male

♀ • by their 4th parity, dams took significantly more time from pairing to delivery than controls

♀ • 2 of 12 dams failed to produce a 4th litter by the end of the breeding trial (90 days after pairing)

♀ • average time from crouching to delivery of each pup was significantly increased relative to controls

♀ • very long labor times were observed in a few individuals

♀ • however, no postpartum cervical histological differences were observed

dystocia ( J:324160 )

♀ • 2 additional females had to be euthanized for dystocia in the first parity

♀ • over 4 parities, 34% of deliveries resulted in either dystocia, stillbirth or both, whereas no adverse outcomes were seen in control dams

♀ • overall, females delivered significantly more stillborn pups than controls; some dead pups appeared constricted or squeezed (flattened)

♀ • 12.5% of pregnancies ended in dystocia

reduced female fertility ( J:324160 )

♀ • the total number of live pups born to dams after 4 parities was 22% lower than in controls

decreased litter size ( J:324160 )

♀ • the number of pups per litter was significantly lower than in control dams independent of parity

behavior/neurological

pup cannibalization ( J:324160 )

♀ • in some cases, only pieces of stillborn pups were observed, likely due to maternal cannibalism

embryo

embryo phenotype ( J:324160 )

♀N • at day 17.5 of pregnancy, dams showed no structural anomalies, size differences or signs of inflammation or hemorrhage in the placenta relative to controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:324160 )

♀N • serum progesterone concentrations were normal at day 3.5 of pregnancy

Genotype
MGI:7333164

cn3

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Rbpj^tm1Hon/Rbpj^tm1Hon
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

embryo

abnormal decidualization ( J:326956 )

♀ • following induction of in vivo artificial decidualization (AD), mice show a reduced decidual response on both 3 and 5 days after AD (AD3 and AD5) based on stimulated to unstimulated uterine horn weight ratio

♀ • on AD5, impaired decidualization is associated with decreased uterine mRNA expression of decidual markers (Bmp2 and Wnt4) and reduced progesterone receptor (Pgr) signaling in the stimulated horn relative to control mice

♀ • consistent with a trend towards decreased mRNA expression of glucose transporter Slc2a1, protein localization SLC2A1 is significantly reduced in the decidual horn esp. within the secondary decidual zone

reproductive system

abnormal decidualization ( J:326956 )

♀ • following induction of in vivo artificial decidualization (AD), mice show a reduced decidual response on both 3 and 5 days after AD (AD3 and AD5) based on stimulated to unstimulated uterine horn weight ratio

♀ • on AD5, impaired decidualization is associated with decreased uterine mRNA expression of decidual markers (Bmp2 and Wnt4) and reduced progesterone receptor (Pgr) signaling in the stimulated horn relative to control mice

♀ • consistent with a trend towards decreased mRNA expression of glucose transporter Slc2a1, protein localization SLC2A1 is significantly reduced in the decidual horn esp. within the secondary decidual zone

Genotype
MGI:7434127

cn4

• Allelic Composition: Men1^tm1.2Zqw/Men1^tm1.2Zqw; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

decreased uterine NK cell number ( J:322043 )

♀ • a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy

abnormal decidualization ( J:322043 )

♀ • although primary decidual zone (PDZ) formation appears normal during early pregnancy, development of the secondary decidual zone (SDZ) is hindered from day 7-8 of pregnancy

♀ • terminal differentiation of stromal cells in the SDZ is impaired, with decreased decidual cell polyploidy and smaller nuclear size noted on day 8 of pregnancy

♀ • immunofluorescence analysis showed a marked reduction in the number of polyploid decidual cells with 4 or more H3K27me3 puncta while staining for PCNA and BrdU is abnormally increased on day 8 of pregnancy

♀ • FACS analysis of DNA content showed that 2N cells are significantly increased while >4N cells are concomitantly decreased on day 8 of pregnancy

♀ • more stromal cells undergo proliferation in the SDZ, with a significantly increased number of PH3+ cells noted on day 8 of pregnancy

♀ • decreased Ptx3 expression in decidual tissues on day 8 of pregnancy leads to aberrant activation of ERK1/2 in the SDZ due to unrestrained FGF2 signal emanating from undifferentiated stromal cells, which blunt Bmp2 induction and decidualization

♀ • after oil-induced artificial decidualization, the decidual response is markedly weakened or absent on day 8 of pseudopregnancy

increased endometrial gland number ( J:322043 )

♀ • immunohistochemical staining of FOXA2 showed an increased number of glands in the lateral areas near the mesometrial pole in the uterine stroma on days 4-6 of pregnancy

impaired embryo implantation ( J:322043 )

♀ • average weight of implantation sites is significantly reduced on days 8 and 9 of pregnancy

♀ • however, blastocyst attachment and implantation appear normal during early pregnancy

increased miscarriage rate ( J:322043 )

♀ • disrupted progression of decidualization leads to miscarriage at mid-gestation, with severe embryo absorption between days 9 and 12 of pregnancy

reduced female fertility ( J:322043 )

♀ • when mated with wild type fertile males, only 25% plug-positive 2-month-old females give birth to offspring vs 83% in control females, indicating severe female subfertility

decreased litter size ( J:322043 )

♀ • when mated with wild type fertile males, females produce a significantly smaller litter size than control females

embryo

abnormal embryo development ( J:322043 )

♀ • embryo development is defective at the post-implantation stage, with severe embryo absorption observed between days 9 and 12 of pregnancy

embryonic growth retardation ( J:322043 )

♀ • embryo growth is retarded in implantation sites on day 8 of pregnancy

abnormal trophoblast giant cell morphology ( J:322043 )

♀ • eccentric expression pattern of trophoblast giant cell marker PL1 indicates shallow trophoblast invasion on day 8 of pregnancy

decreased uterine NK cell number ( J:322043 )

♀ • a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy

abnormal placenta development ( J:322043 )

♀ • expression of COX2 in the presumptive site of placentation is disordered on day 8 of pregnancy; placentation is obviously abnormal starting on day 9

abnormal decidualization ( J:322043 )

♀ • although primary decidual zone (PDZ) formation appears normal during early pregnancy, development of the secondary decidual zone (SDZ) is hindered from day 7-8 of pregnancy

♀ • terminal differentiation of stromal cells in the SDZ is impaired, with decreased decidual cell polyploidy and smaller nuclear size noted on day 8 of pregnancy

♀ • immunofluorescence analysis showed a marked reduction in the number of polyploid decidual cells with 4 or more H3K27me3 puncta while staining for PCNA and BrdU is abnormally increased on day 8 of pregnancy

♀ • FACS analysis of DNA content showed that 2N cells are significantly increased while >4N cells are concomitantly decreased on day 8 of pregnancy

♀ • more stromal cells undergo proliferation in the SDZ, with a significantly increased number of PH3+ cells noted on day 8 of pregnancy

♀ • decreased Ptx3 expression in decidual tissues on day 8 of pregnancy leads to aberrant activation of ERK1/2 in the SDZ due to unrestrained FGF2 signal emanating from undifferentiated stromal cells, which blunt Bmp2 induction and decidualization

♀ • after oil-induced artificial decidualization, the decidual response is markedly weakened or absent on day 8 of pseudopregnancy

cellular

abnormal DNA methylation ( J:322043 )

♀ • reduction of Bmp2 expression caused by aberrant activation of the ERK1/2 signaling pathway disrupts development of the SDZ due to disorganized genomic H3K4me3 modification

endocrine/exocrine glands

decreased uterine NK cell number ( J:322043 )

♀ • a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy

increased endometrial gland number ( J:322043 )

♀ • immunohistochemical staining of FOXA2 showed an increased number of glands in the lateral areas near the mesometrial pole in the uterine stroma on days 4-6 of pregnancy

growth/size/body

embryonic growth retardation ( J:322043 )

♀ • embryo growth is retarded in implantation sites on day 8 of pregnancy

hematopoietic system

decreased uterine NK cell number ( J:322043 )

♀ • a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy

immune system

decreased uterine NK cell number ( J:322043 )

♀ • a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy

Genotype
MGI:6854709

cn5

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

abnormal decidualization ( J:165229 )

♀ • although blastocysts can attach to the uterine lumen and initiate a decidual response, the decidual region and size of the embryos is significantly smaller on day 5.5 of natural pregnancy

♀ • after induction of artificial decidualization, stimulated horn weight:unstimulated horn weight ratio is significantly lower than that in controls

♀ • decidualization defect can be partially rescued by intrauterine injection of recombinant leukemia inhibitory factor (LIF) prior to the initiation of the decidual response

abnormal endometrial gland development ( J:165229 )

♀ • uteri of 8-wk-old females show a severe defect in endometrial gland development

♀ • loss of endometrial glands results in a marked reduction of leukemia inhibitory factor (Lif) expression on day 3.5 of pseudopregnancy

decreased endometrial gland number ( J:165229 )

♀ • nonpregnant uteri of 8-wk-old females show a severe reduction in the number of endometrial glands relative to control uteri

abnormal embryo invasion ( J:165229 )

♀ • on day 5.5 of pregnancy, embryos fail to exhibit invasion into the uterine stroma through the epithelium

impaired embryo implantation ( J:165229 )

♀ • on day 5.5 of pregnancy, the number of implantation sites is significantly lower than that in control uteri

abnormal uterus physiology ( J:165229 )

♀ • uterus is unable to support embryo invasion and undergo an experimentally induced decidual response with exogenous steroid hormones

reduced female fertility ( J:165229 )

♀ • when mated to wild-type males for a period of 6 months, females exhibit severe subfertility, with significantly fewer litters, pups per litter and total pups born relative to control females

decreased litter size ( J:165229 )

♀ • females produce significantly fewer pups per litter than control females

embryo

abnormal decidualization ( J:165229 )

♀ • although blastocysts can attach to the uterine lumen and initiate a decidual response, the decidual region and size of the embryos is significantly smaller on day 5.5 of natural pregnancy

♀ • after induction of artificial decidualization, stimulated horn weight:unstimulated horn weight ratio is significantly lower than that in controls

♀ • decidualization defect can be partially rescued by intrauterine injection of recombinant leukemia inhibitory factor (LIF) prior to the initiation of the decidual response

endocrine/exocrine glands

abnormal endometrial gland development ( J:165229 )

♀ • uteri of 8-wk-old females show a severe defect in endometrial gland development

♀ • loss of endometrial glands results in a marked reduction of leukemia inhibitory factor (Lif) expression on day 3.5 of pseudopregnancy

decreased endometrial gland number ( J:165229 )

♀ • nonpregnant uteri of 8-wk-old females show a severe reduction in the number of endometrial glands relative to control uteri

Genotype
MGI:3813635

cn6

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

reproductive system phenotype ( J:139053 )

N • unlike mice with conditional loss of Pten, endometrial morphology and histology appear normal through 5 months of age

Genotype
MGI:5583019

cn7

• Allelic Composition: Apc^tm1Rsmi/Apc^tm1Rsmi; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

neoplasm

increased reproductive system tumor incidence ( J:210095 )

• 62.5% of mice develop endometrioid tubal tumors in distal and fimbrial parts of the oviduct showing severe nuclear atypia, subnuclear vacuolization, abnormal proliferation, complete loss of normal oviduct architecture and compression of the lumen

• tumors resemble human endometrioid tubal cancer

increased ovary tumor incidence ( J:210095 )

• 27.9% of mice develop endometrioid ovarian tumors which may originate form the endometrioid ovarian cysts, resembling human endometrioid ovarian cancer

increased granulosa cell tumor incidence ( J:210095 )

• 1 of 43 mice develop a granulosa cell tumor which is distinct from the endometrioid tubal cancer

reproductive system

increased reproductive system tumor incidence ( J:210095 )

• 62.5% of mice develop endometrioid tubal tumors in distal and fimbrial parts of the oviduct showing severe nuclear atypia, subnuclear vacuolization, abnormal proliferation, complete loss of normal oviduct architecture and compression of the lumen

• tumors resemble human endometrioid tubal cancer

increased ovary tumor incidence ( J:210095 )

• 27.9% of mice develop endometrioid ovarian tumors which may originate form the endometrioid ovarian cysts, resembling human endometrioid ovarian cancer

increased granulosa cell tumor incidence ( J:210095 )

• 1 of 43 mice develop a granulosa cell tumor which is distinct from the endometrioid tubal cancer

abnormal internal female genitalia morphology ( J:210095 )

• 9.4% of mice show extraovarian endometrioid lesions within the utero-ovarian ligament, next to the tubal and ovarian tumors

ovary cyst ( J:210095 )

• 16.3% of mice show ovarian endometrioid cysts, mostly in younger mice

abnormal oviduct morphology ( J:210095 )

• 87.2% of mice exhibit tubular intraepithelial lesions in the epithelium of the distal oviduct and fimbriae

• lesions show loss of cilia, bulging of cells into the lumen, layering and suspicious stratification of cells, and rounding and hyperchromatization of the nucleus

• 20% of mice develop glandular transformation of the normal papillary architecture of the oviduct characterized by glandular growth, loss of cilia, and general loss of normal cellular morphology

endometrium hyperplasia ( J:210095 )

• presence of extraovarian endometrioid lesions coincide with lesions found in the oviduct and ovary

endocrine/exocrine glands

increased ovary tumor incidence ( J:210095 )

• 27.9% of mice develop endometrioid ovarian tumors which may originate form the endometrioid ovarian cysts, resembling human endometrioid ovarian cancer

increased granulosa cell tumor incidence ( J:210095 )

• 1 of 43 mice develop a granulosa cell tumor which is distinct from the endometrioid tubal cancer

ovary cyst ( J:210095 )

• 16.3% of mice show ovarian endometrioid cysts, mostly in younger mice

growth/size/body

ovary cyst ( J:210095 )

• 16.3% of mice show ovarian endometrioid cysts, mostly in younger mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:210095

Genotype
MGI:4946386

cn8

• Allelic Composition: Wnt11^tm1.1Khay/Wnt11^tm1.2Khay; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

reproductive system

increased endometrial gland number ( J:170159 )

♀ • at P10, the number of endometrial glands is increased compared to in wild-type mice

abnormal uterus physiology ( J:170159 )

♀ • at P10, cell proliferation in the uterine stroma is increased compared to in wild-type mice

♀ • however, proliferation is normal at P15 and P20

endocrine/exocrine glands

increased endometrial gland number ( J:170159 )

♀ • at P10, the number of endometrial glands is increased compared to in wild-type mice

Genotype
MGI:5285205

cn9

• Allelic Composition: Wnt7a^tm1.1Tesp/Wnt7a^tm1.1Tesp; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * SJL

reproductive system

absent endometrial glands ( J:175291 )

♀ • no endometrial glands develop

abnormal postimplantation uterine environment ( J:175291 )

♀ • uteri fail to support blastocyst implantation unlike in wild-type mice

female infertility ( J:175291 )

♀

endocrine/exocrine glands

absent endometrial glands ( J:175291 )

♀ • no endometrial glands develop

Genotype
MGI:3716551

cn10

• Allelic Composition: Ncoa2^tm1.1Ipc/Ncoa2^tm1.1Ipc; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

embryo

abnormal decidualization ( J:117006 )

♀ • uterus displays only partial decidual response to the deciduogenic stimulus estradiol + progesterone

reproductive system

reproductive system phenotype ( J:117006 )

N • gonadotropin-treated ovaries ovulate comparably to wild-type, showing similar oocyte production

N • epithelial proliferation in estradiol-treated ovarectomized uteri from mutants is similar to wild-type

abnormal decidualization ( J:117006 )

♀ • uterus displays only partial decidual response to the deciduogenic stimulus estradiol + progesterone

failure of embryo implantation ( J:117006 )

♀ • implantation sites are absent at 5.5 days post-coitum

female infertility ( J:117006 )

♀ • females are infertile, despite normal mating behavior and presence of copulatory plugs; no litters were produced during six months of observation

endocrine/exocrine glands

abnormal branching of the mammary ductal tree ( J:117006 )

♀ • after a 3-week estradiol + progesterone treatment regime, full ductal side-branching and alveogenesis does not occur in mutant mammary glands in contrast to wild-type

integument

abnormal branching of the mammary ductal tree ( J:117006 )

♀ • after a 3-week estradiol + progesterone treatment regime, full ductal side-branching and alveogenesis does not occur in mutant mammary glands in contrast to wild-type

Genotype
MGI:4944273

cn11

• Allelic Composition: Errfi1^tm1Jwj/Errfi1^tm1Jwj; Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:162027 )

• survival time of double mutants is shorter than either single mutant, with mice dying by 16 weeks of age

reproductive system

increased endometrial carcinoma incidence ( J:162027 )

♀ • development of endometrial cancer is accelerated compared to either single mutant

abnormal endometrium morphology ( J:162027 )

♀ • decrease in the number of apoptotic cells in the endothelium epithelium compared to single Pten mutants

♀ • proliferation is increased in the endothelium epithelium

endometrium hyperplasia ( J:162027 )

♀ • mutants exhibit endometrial hyperplasia at 2 weeks of age and develop endometrial adenocarcinoma at 4 weeks of age

♀ • however, myometrial hyperplasia is not observed in the uteri of mutants

increased uterus weight ( J:162027 )

♀ • increase in uterine weight at 2 weeks of age, with weight at 4 weeks greater than in single Pten mutants

neoplasm

increased metastatic potential ( J:162027 )

• mutants exhibit distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, colon and pancreas

increased endometrial carcinoma incidence ( J:162027 )

♀ • development of endometrial cancer is accelerated compared to either single mutant

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometrial cancer		DOID:1380	OMIM:608089	J:162027

Genotype
MGI:4944272

cn12

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:218222 )

♀ • mice display a progressive decline in survival due to the development of endometrial cancer; all mice die by ~50 weeks of age

reproductive system

increased endometrial carcinoma incidence ( J:162027 , J:218222 )

♀ • mice develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age (J:162027)

♀ • mice develop endometrial adenocarcinoma at 2 and 3 months of ages as characterized by neoplastic endometrial glands invading through the myometrium (J:218222)

♀ • treatment with U0126, an effective inhibitor of MAPK/ERK kinase, suppresses endometrial cancer progression, as shown by the arrest of tumors at the hyperplastic or normal stage (J:218222)

endometrium hyperplasia ( J:162027 )

♀ • mice exhibit endometrial hyperplasia at 4 weeks of age

decreased uterus weight ( J:218222 )

♀ • mice treated with U0126, an effective inhibitor of MAPK/ERK kinase, display a significant decrease in uterine weight relative to mice treated with vehicle

increased uterus weight ( J:162027 , J:218222 )

♀ • increase in uterine weight at 2 weeks of age (J:162027)

♀ • at 3 months of age, mice show a significant increase in uterine/body weight ratio relative to controls (J:218222)

abnormal uterus physiology ( J:162027 )

♀ • proliferation is increased in the endothelium epithelium

neoplasm

increased endometrial carcinoma incidence ( J:162027 , J:218222 )

♀ • mice develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age (J:162027)

♀ • mice develop endometrial adenocarcinoma at 2 and 3 months of ages as characterized by neoplastic endometrial glands invading through the myometrium (J:218222)

♀ • treatment with U0126, an effective inhibitor of MAPK/ERK kinase, suppresses endometrial cancer progression, as shown by the arrest of tumors at the hyperplastic or normal stage (J:218222)

increased papilloma incidence ( J:218222 )

♀ • mice develop vaginal papillomas

Genotype
MGI:5901907

cn13

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Ror1^tm1.1Meg/Ror1^tm1.1Meg; Ror2^tm1.1Meg/Ror2^tm1.1Meg
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

reproductive system

abnormal maternal decidual layer morphology ( J:233595 )

♀ • abnormal primary decidual zone (PDZ) development at 6 dpc

♀ • PDZ was absent in some implantation sites with the embryo entrapped within the intact epithelium at 6 dpc

abnormal embryo attachment ( J:233595 )

♀ • uteri either failed to show or had very weak endometrial vascular permeability at the site of blastocyst attachment at 5 dpc

♀ • unattached blastocysts were recovered from uteri at 5 dpc

♀ • defects in crypt formation

♀ • some blastocysts situated within the primary lumen

reduced female fertility ( J:233595 )

♀ • only 29% of plug-positive females produce a (small) litter

♀ • high resorption rates on 12 dpc

decreased litter size ( J:233595 )

♀ • in the few fertile mice

embryo

abnormal maternal decidual layer morphology ( J:233595 )

♀ • abnormal primary decidual zone (PDZ) development at 6 dpc

♀ • PDZ was absent in some implantation sites with the embryo entrapped within the intact epithelium at 6 dpc

Genotype
MGI:5780554

cn14

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-Errfi1)Jwj}/?; Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:218222 )

♀ • mice exhibit significantly increased survival time relative to mice that are homozygous for Pten^tm1Hwu and heterozygous for Pgr^tm2(cre)Lyd, with >50% of mice still viable at 64 weeks of age

♀ • mice do not die due to the development of endometrial cancer

reproductive system

endometrium hyperplasia ( J:218222 )

♀ • mice exhibit endometrial hyperplasia at 2 months but not at 3 months of age

♀ • however, endometrial adenocarcinoma with invasion into the myometrium is not observed due to inhibition of ERK1/2 phosphorylation

increased uterus weight ( J:218222 )

♀ • at 3 months of age, mice show a significantly reduced increase in uterine/body weight ratio relative to mice that are homozygous for Pten^tm1Hwu and heterozygous for Pgr^tm2(cre)Lyd

abnormal uterus physiology ( J:218222 )

♀ • at 2 months of age, mice show a significantly reduced uterine epithelial cell proliferation relative to mice that are homozygous for Pten^tm1Hwu and heterozygous for Pgr^tm2(cre)Lyd

neoplasm

increased papilloma incidence ( J:218222 )

♀ • mice develop vaginal papillomas

Genotype
MGI:3813633

cn15

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:139053 )

• impaired survival is seen beginning around 5 months of age

reproductive system

increased endometrial carcinoma incidence ( J:139053 )

♀ • hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age

endometrium hyperplasia ( J:139053 )

♀ • by P10, luminal and glandular epithelial hyperplasia are seen

neoplasm

increased endometrial carcinoma incidence ( J:139053 )

♀ • hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometrial cancer		DOID:1380	OMIM:608089	J:139053

Genotype
MGI:5474794

cn16

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-NR2F1)Mjts}/Gt(ROSA)26Sor⁺; Nr2f2^tm2.1Tsa/Nr2f2^tm2.1Tsa; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

reproductive system

reproductive system phenotype ( J:162256 )

♀N • uterus defects observed in Nr2f2^tm2.1Tsa/Nr2f2^tm2.1Tsa Pgr^tm2(cre)Lyd/Pgr⁺ mice are rescued

Genotype
MGI:5474795

cn17

• Allelic Composition: Nr2f2^tm2.1Tsa/Nr2f2^tm2.1Tsa; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

reproductive system

female infertility ( J:162256 )

♀ • due to defective embryo attachment and decidualization

Genotype
MGI:5901913

cn18

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Wnt5a^tm1.1Tpy/Wnt5a^tm1.1Tpy
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

reproductive system phenotype ( J:233595 )

♀N • both genes are expressed in ovaria, but ovulation, fertilization, preimplantation embryo development and hormone production are normal in conditional loss-of-function females

abnormal uterus morphology ( J:233595 )

♀ • persistent apicobasal polarity in the luminal epithelium with increased cell heights and retention of glycosylated microvilli on the apical surface

abnormal maternal decidual layer morphology ( J:233595 )

♀ • abnormal primary decidual zone (PDZ) development at 6 dpc

♀ • PDZ was absent in some implantation sites with the embryo entrapped within the intact epithelium at 6 dpc

abnormal embryo attachment ( J:233595 )

♀ • uteri either failed to show or had very weak endometrial vascular permeability at the site of blastocyst attachment at 5 dpc

♀ • unattached blastocysts were recovered from uteri at 5 dpc

♀ • defects in crypt formation

♀ • some blastocysts situated within the primary lumen

abnormal uterine-embryonic axis ( J:233595 )

♀ • inappropriate mesometrial-antimesometrial (M-AM) orientation of implantation sites at 5, 6 and 8 dpc: closer to M pole instead of at AM pole

♀ • ratio of M-AM axis length to anterior-posterior (A-P) axis length is reduced by ~25% resulting in a more spherical morphology at 8 dpc

impaired embryo implantation ( J:233595 )

♀ • uteri either failed to show or had very weak endometrial vascular permeability at the site of blastocyst attachment at 5 dpc

♀ • different sizes of implantation sites at 8 dpc

impaired spacing of implantation sites ( J:233595 )

♀ • implantation sites were often irregularly spaced at 5 and 8 dpc

twin decidual capsule ( J:233595 )

♀ • two embryos closely apposed within one implantation site

reduced female fertility ( J:233595 )

♀ • only 33% of plug-positive females produce a (small) litter

♀ • high resorption rates

decreased litter size ( J:233595 )

♀ • in the few fertile mice

embryo

abnormal trophoblast giant cell proliferation ( J:233595 )

♀ • clusters of Prl3d1-positive trophoblast giant cells in implantation sites in lieu of the embryo proper at 10 dpc

abnormal embryo development ( J:233595 )

♀ • increasing numbers of resorption sites on 10 and 12 dpc

♀ • absent or substantially smaller embryos in many implantation sites from 10 dpc

abnormal placenta morphology ( J:233595 )

♀ • in surviving implantation sites at 12 dpc

♀ • disrupted placental development from 10 dpc

abnormal maternal decidual layer morphology ( J:233595 )

♀ • abnormal primary decidual zone (PDZ) development at 6 dpc

♀ • PDZ was absent in some implantation sites with the embryo entrapped within the intact epithelium at 6 dpc

decreased placental labyrinth size ( J:233595 )

♀ • Gcm1-positive syncytiotrophoblasts in the labyrinth failed to elongate, suggesting disrupted secondary branching morphogenesis of placental villi at 12 dpc

cellular

abnormal trophoblast giant cell proliferation ( J:233595 )

♀ • clusters of Prl3d1-positive trophoblast giant cells in implantation sites in lieu of the embryo proper at 10 dpc

Genotype
MGI:6275549

cn19

• Allelic Composition: Gt(ROSA)26Sor^{tm2(CAG-Nr5a1)Fjd}/Gt(ROSA)26Sor⁺; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

embryo

abnormal decidualization ( J:269597 )

♀ • ovariectomized mice show an absent decidual response in uteri indicating that the endometrium is unable to undergo decidualization

endocrine/exocrine glands

abnormal endometrial gland morphology ( J:269597 )

♀ • abnormal morphology of uterine glands, including fluid-filled glands

abnormal endometrial gland development ( J:269597 )

♀ • marker analysis indicates that uterine glands are more differentiated, with a higher proportion of glandular to luminal cells

enlarged endometrial glands ( J:269597 )

♀ • uterine glands are twice the size in cell number as controls

immune system

uterus inflammation ( J:269597 )

♀ • mice show an increased presence of neutrophils in uteri

reproductive system

abnormal decidualization ( J:269597 )

♀ • ovariectomized mice show an absent decidual response in uteri indicating that the endometrium is unable to undergo decidualization

uterus inflammation ( J:269597 )

♀ • mice show an increased presence of neutrophils in uteri

abnormal uterus morphology ( J:269597 )

♀ • adult females in which endometriosis is induced by autotransplantation of uterine tissue to the mesenteric membrane show an increase in size of ectopic lesions; lesions show decreased epithelial cell proliferation, luminal epithelial cells that appear cuboidal instead of columnar, and most of the lesion volume is comprised of a large, fluid-filled central lumen

uterus cyst ( J:269597 )

♀ • females bred with wild-type males contain numerous cystic uterine glands

abnormal endometrium morphology ( J:269597 )

♀ • endometrial architecture is altered in bred females

abnormal endometrial gland morphology ( J:269597 )

♀ • abnormal morphology of uterine glands, including fluid-filled glands

abnormal endometrial gland development ( J:269597 )

♀ • marker analysis indicates that uterine glands are more differentiated, with a higher proportion of glandular to luminal cells

enlarged endometrial glands ( J:269597 )

♀ • uterine glands are twice the size in cell number as controls

enlarged uterine horn ( J:269597 )

♀ • females bred with wild-type males show enlarged and translucent uterine horns

female infertility ( J:269597 )

♀ • females bred with wild-type males do not reproduce

♀ • however, 3 week old females stimulated with gonadotrophins and mated with wild-type males exhibit a normal number of fertilized ova, normal progesterone and estradiol serum levels and normal uterine and ovarian estradiol levels, indicating normal ovarian and luteal function

growth/size/body

uterus cyst ( J:269597 )

♀ • females bred with wild-type males contain numerous cystic uterine glands

Genotype
MGI:5641710

cn20

• Allelic Composition: Tsc2^tm1.1Mjg/Tsc2^tm1.1Mjg; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

increased endometrial gland number ( J:221228 )

♀

increased uterus leiomyoma incidence ( J:221228 )

♀ • mice exhibit myometrial overgrowth, developing tumors consistent with leiomyomas by 24 weeks of age

endometrium hyperplasia ( J:221228 )

♀ • increase in endometrial proliferation, with more endometrial glands and irregular luminal epithelium in uteri

abnormal myometrium morphology ( J:221228 )

♀ • increase in myometrial proliferation at 12 weeks of age

♀ • myometrium is thickened with rough borders and irregular, disoriented cells

♀ • ovariectomy in 4 week old mice prevents abnormal uterine growth and estrogen stimulates myometrial proliferation in ovariectomized females

♀ • treatment with aromatase inhibitor, letrozole, for 8 weeks starting at 4 weeks of age, reduces myometrial proliferation

enlarged uterus ( J:221228 )

♀ • starting at 6 weeks of age, mice start to show uterine enlargement, and uterine size and weight are larger at 12 weeks of age

♀ • treatment with rapamycin at 4 weeks of age for 8 weeks completely prevents abnormal growth in the uterus

increased uterus weight ( J:221228 )

♀ • at 12 weeks of age

neoplasm

increased uterus leiomyoma incidence ( J:221228 )

♀ • mice exhibit myometrial overgrowth, developing tumors consistent with leiomyomas by 24 weeks of age

increased metastatic potential ( J:221228 )

♀ • tumors in the lungs originate from the lymphatics, suggesting that lung tumors are metastatic from the uterus

increased lung tumor incidence ( J:221228 )

♀ • most females that reach 31 weeks of age or older exhibit myometrial tumors in the lungs, suggesting lymphangioleiomyomatosis

cardiovascular system

internal hemorrhage ( J:221228 )

♀ • 24 week old mice show appreciably larger uteri, with continued endometrial overgrowth and internal bleeding

endocrine/exocrine glands

increased endometrial gland number ( J:221228 )

♀

muscle

increased uterus leiomyoma incidence ( J:221228 )

♀ • mice exhibit myometrial overgrowth, developing tumors consistent with leiomyomas by 24 weeks of age

respiratory system

increased lung tumor incidence ( J:221228 )

♀ • most females that reach 31 weeks of age or older exhibit myometrial tumors in the lungs, suggesting lymphangioleiomyomatosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
uterine fibroid		DOID:13223	OMIM:150699	J:221228

Genotype
MGI:6870538

cn21

• Allelic Composition: Klf5^tm1Jaw/Klf5^tm1Jaw; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

abnormal decidualization ( J:179912 )

♀ • although stromal cells were able to initiate decidualization, the decidual response was severely impaired with smaller decidual sizes and no viable embryos present in implantation chambers on day 8 of pregnancy

♀ • after oil-induced artificial decidualization, fold increase in uterine weight of infused-to-non-infused horns was significantly less than that in controls on day 8 of pseudopregnancy

abnormal embryo attachment ( J:179912 )

♀ • on day 5 of pregnancy, COX2 expression was absent in the uterine luminal epithelium but present in stromal cells at the blastocyst site, suggesting that poor embryo attachment might be due to aberrant COX2 expression

failure of embryo implantation ( J:179912 )

♀ • although embryos did develop to blastocysts in uteri, most failed to implant or showed defective implantation

♀ • blastocysts remained entrapped within the luminal epithelium past the window of implantation

impaired embryo implantation ( J:179912 )

♀ • on day 5 of pregnancy, 8 of 11 females exhibited implantation sites but the number of implantation sites per female was significantly lower than that in control females

♀ • on day 6, the uterine luminal epithelium around the implantation chamber failed to degenerate and show loss of E-cadherin, unlike in control uteri

♀ • on day 7, implanted embryos were either very small or absorbed; some embryos were still surrounded by epithelial cells but showed signs of degeneration

♀ • most implantation sites showed continued growth until day 8 but the number of sites on day 8 was similar to that on days 5 and 6

♀ • on day 8, the weight of implantation sites was significantly lower than that in control females

♀ • however, initiation of embryo-uterine interplay was not delayed

abnormal uterine receptivity ( J:179912 )

♀ • uteri are largely unfavorable for normal implantation

♀ • however, uterine responsiveness to estrogen and P4 was normal

female infertility ( J:179912 )

♀ • most females were found to be infertile

reduced female fertility ( J:179912 )

♀ • after mating with wild-type males, only 2 of 10 plug-positive females produced pups

decreased litter size ( J:179912 )

♀ • 2 of 10 plug-positive females tested gave birth to only 2 and 3 pups/litter whereas control females delivered 8 pups/litter

embryo

abnormal decidualization ( J:179912 )

♀ • although stromal cells were able to initiate decidualization, the decidual response was severely impaired with smaller decidual sizes and no viable embryos present in implantation chambers on day 8 of pregnancy

♀ • after oil-induced artificial decidualization, fold increase in uterine weight of infused-to-non-infused horns was significantly less than that in controls on day 8 of pseudopregnancy

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:179912 )

♀N • females show normal serum estrogen (E2) and progesterone (P4) levels on day 4 of pregnancy

Genotype
MGI:7264294

cn22

• Allelic Composition: Gata2^tm1Sac/Gata2^tm1Sac; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

abnormal decidualization ( J:240902 )

♀ • females failed to undergo a decidual reaction in response to estradiol (E2) plus progesterone (P4) treatment, with no increase in uterine size and weight or change in stromal cell shape and alkaline phosphatase staining in the stimulated horn on day 2 and day 5 after decidual stimulation

♀ • mRNA levels of several genes critical for proliferation and differentiation of endometrial stromal cells were significantly reduced in the stimulated horn 5 days after stimulation

abnormal endometrium morphology ( J:240902 )

♀ • in response to E2 treatment, uteri of ovariectomized (OVX) mice showed alterations in endometrial epithelial morphology resulting in a transition from a simple epithelium to a stratified squamous epithelium with increased TRP63 expression

failure of embryo implantation ( J:240902 )

♀ • no embryo implantation sites were detected at day 5.5 of pregnancy

♀ • however, serum P4 levels were normal at day 5.5 of pregnancy

abnormal uterus physiology ( J:240902 )

♀ • uteri of OVX mice showed significantly reduced progesterone receptor (PGR) protein levels in the luminal and glandular epithelia at both baseline and in response to P4 stimulation

♀ • uteri of OVX mice showed a complete loss of P4-dependent induction of PGR-regulated genes Areg and Cyp26a1 as well as decreased Ihh mRNA expression at both baseline and in response to P4, indicating attenuated P4 signaling

♀ • P4 treatment failed to regulate 97% of P4 response genes in OVX uteri; many of the remaining P4 response genes showed reduced magnitude on change of gene expression in response to P4

♀ • day 3.5 pseudopregnancy uteri showed uninhibited estrogen signaling with higher E2 signaling activities in the absence of elevated ESR1 levels and abnormally high uterine epithelial proliferation, unlike control uteri where epithelial proliferation was high at day 2.5 but reduced at day 3.5

♀ • uteri of OVX mice showed ectopic expression of TRP63 in a layer of cells, morphologically similar to basal cells, underneath the columnar luminal epithelia and a cancer-related molecular profile

female infertility ( J:240902 )

♀ • all 8-week-old female mice mated with wild-type males failed to produce offspring over a 6-month breeding period

♀ • however, females subjected to a superovulatory regimen ovulated a similar number of eggs as control females

embryo

abnormal decidualization ( J:240902 )

♀ • females failed to undergo a decidual reaction in response to estradiol (E2) plus progesterone (P4) treatment, with no increase in uterine size and weight or change in stromal cell shape and alkaline phosphatase staining in the stimulated horn on day 2 and day 5 after decidual stimulation

♀ • mRNA levels of several genes critical for proliferation and differentiation of endometrial stromal cells were significantly reduced in the stimulated horn 5 days after stimulation

Genotype
MGI:5299193

cn23

• Allelic Composition: Phb2^tm2.1Katz/Phb2^tm2.1Katz; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

reproductive system phenotype ( J:178347 )

N • mice exhibit normal ovarian function, including follicle maturation, ovulation, corpora lutea formation, and estrous cycle

integument

abnormal mammary gland morphology ( J:178347 )

♀ • at 15 weeks, mice exhibit severe defects in mammary gland morphogenesis

abnormal mammary gland duct morphology ( J:178347 )

♀ • during puberty, mammary ductal morphogenesis is severely impaired compared to in control mice

♀ • terminal end buds are very small and not developed compared to in control mice

♀ • at 24 weeks, the ductal network barely invades the fat pad

endocrine/exocrine glands

abnormal mammary gland morphology ( J:178347 )

♀ • at 15 weeks, mice exhibit severe defects in mammary gland morphogenesis

abnormal mammary gland duct morphology ( J:178347 )

♀ • during puberty, mammary ductal morphogenesis is severely impaired compared to in control mice

♀ • terminal end buds are very small and not developed compared to in control mice

♀ • at 24 weeks, the ductal network barely invades the fat pad

Genotype
MGI:5299191

cn24

• Allelic Composition: Phb2^tm2.1Katz/Phb2⁺; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

endocrine/exocrine glands

abnormal mammary gland duct morphology ( J:178347 )

♀ • during puberty, mammary ductal morphogenesis is accelerated with increased ductal length compared to in control mice

♀ • the number of terminal end buds is increased compared to in control mice

integument

abnormal mammary gland duct morphology ( J:178347 )

♀ • during puberty, mammary ductal morphogenesis is accelerated with increased ductal length compared to in control mice

♀ • the number of terminal end buds is increased compared to in control mice

Genotype
MGI:3850221

cn25

• Allelic Composition: Errfi1^tm1Jwj/Errfi1^tm1Jwj; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

abnormal uterus morphology ( J:150007 )

♀ • mice exhibit an increase in the ratio of gland to stroma compared to in Errfi1^tm1Jwj homozygotes

♀ • however, the myometrium is not enlarged

increased endometrial gland number ( J:150007 )

♀ • the number of endometrial glands is increased compared to in Errfi1^tm1Jwj homozygotes due to increased proliferation

♀ • ovariectomized mice treated with E2 and P4 exhibit increased vascularization compared to in similarly treated Errfi1^tm1Jwj homozygotes

increased endometrial carcinoma incidence ( J:150007 )

♀ • E2-treated, ovariectomized mice develop endometrial cancer unlike similarly treated Errfi1^tm1Jwj homozygotes

♀ • however, ovariectomized mice treated with E2 and P4 do not develop endometrial cancer

♀ • neoplastic endometrial glands invade adjacent structures such as the colon, pancreas, and skeletal muscle

endometrium hyperplasia ( J:150007 )

♀ • mice develop endometrial hyperplasia

increased uterus weight ( J:150007 )

♀ • at 5 months, uterine wet weight is increased compared to in Errfi1^tm1Jwj homozygotes

♀ • after 3 months, ovectamized mice treated with E2 and P4 exhibit increased uterus weight compared to in similarly treated Errfi1^tm1Jwj homozygotes

female infertility ( J:150007 )

♀ • despite normal oocyte numbers and uterine environment, female mice are infertile

neoplasm

increased endometrial carcinoma incidence ( J:150007 )

♀ • E2-treated, ovariectomized mice develop endometrial cancer unlike similarly treated Errfi1^tm1Jwj homozygotes

♀ • however, ovariectomized mice treated with E2 and P4 do not develop endometrial cancer

♀ • neoplastic endometrial glands invade adjacent structures such as the colon, pancreas, and skeletal muscle

endocrine/exocrine glands

increased endometrial gland number ( J:150007 )

♀ • the number of endometrial glands is increased compared to in Errfi1^tm1Jwj homozygotes due to increased proliferation

♀ • ovariectomized mice treated with E2 and P4 exhibit increased vascularization compared to in similarly treated Errfi1^tm1Jwj homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometrial cancer		DOID:1380	OMIM:608089	J:150007

Genotype
MGI:6827353

cn26

• Allelic Composition: Ezh2^tm2Sho/Ezh2^tm2Sho; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

decreased uterine NK cell number ( J:290765 )

♀ • number of uterine natural killer cells is reduced in E8.5 decidual basalis

abnormal endometrium morphology ( J:290765 )

♀ • at 8 months of age, the endometrium shows pathological changes resembling human endometrial hyperplasia

♀ • however, the myometrial layers remain intact

abnormal endometrial gland morphology ( J:290765 )

♀ • at 8 months of age, cystic dilation of endometrial glands containing eosin-stained substance is observed

♀ • endometrial glands are variable in size and some contain stratified epithelial layers with nuclear atypia in some cases

♀ • FOXA2 expression is reduced or partially lost in some glands at 2 months of age

increased endometrial gland number ( J:290765 )

♀ • a slight level of endometrial gland crowding is noted in discrete regions, with intervening uterine stroma among glands shown to be sparse

endometrium hyperplasia ( J:290765 )

♀ • at 5 to 8 months of age, endometrial hyperplasia is observed in nulliparous female mice

♀ • Ki-67 staining is increased in some abnormal endometrial glands or cystic glandular structures

enlarged uterine horn ( J:290765 )

♀ • weight of uterine horns is increased, even at 1 month of age (before sexual maturity)

abnormal uterine epithelium development ( J:290765 )

♀ • at 1 and 2 months of age, uterus shows focal expression of basal cell markers KRT14 and TRP63 in a cell layer beneath luminal and/or glandular epithelial cells indicating focal formation of stratified uterine epithelium, unlike in wild-type uteri

♀ • by 8 months of age, epithelial stratification is more extensive as shown by the presence of cells positively staining for KRT14, KRT5, KRT6A, and TRP63

♀ • partial loss of FOXA2 expression is observed in the glandular epithelia at 2 months and no FOXA2 expression is detected in KRT14+ epithelial cells lining the luminal/glandular epithelia at 8 months

♀ • basal-like epithelial cells (KRT14+ but KRT8-) lining some KRT8+ epithelial cells are detected at 8 months, and mRNA expression of basal cell markers is increased in uterine epithelia isolated at 1 month of age, indicating production of basal-like epithelial cells or a cell population expressing basal markers in the uterus

abnormal parturition ( J:290765 )

♀ • females display parturition defects

dystocia ( J:290765 )

♀ • ~64% of females show signs of dystocia or difficulty in labor

reduced female fertility ( J:290765 )

♀ • females mated with fertile males for a period of 6 months yield a decreased number of litters and litter size relative to controls

♀ • however, blastocysts can be retrieved from uteri at ~E3.5 and implantation sites can be found at E8.5

decreased litter size ( J:290765 )

♀ • females mated with fertile males produce a smaller litter size than controls

embryo

decreased uterine NK cell number ( J:290765 )

♀ • number of uterine natural killer cells is reduced in E8.5 decidual basalis

endocrine/exocrine glands

decreased uterine NK cell number ( J:290765 )

♀ • number of uterine natural killer cells is reduced in E8.5 decidual basalis

abnormal endometrial gland morphology ( J:290765 )

♀ • at 8 months of age, cystic dilation of endometrial glands containing eosin-stained substance is observed

♀ • endometrial glands are variable in size and some contain stratified epithelial layers with nuclear atypia in some cases

♀ • FOXA2 expression is reduced or partially lost in some glands at 2 months of age

increased endometrial gland number ( J:290765 )

♀ • a slight level of endometrial gland crowding is noted in discrete regions, with intervening uterine stroma among glands shown to be sparse

hematopoietic system

decreased uterine NK cell number ( J:290765 )

♀ • number of uterine natural killer cells is reduced in E8.5 decidual basalis

immune system

decreased uterine NK cell number ( J:290765 )

♀ • number of uterine natural killer cells is reduced in E8.5 decidual basalis

Genotype
MGI:5901730

cn27

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-Wnt5a,-AcGFP)Skde}/Gt(ROSA)26Sor⁺; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

reproductive system phenotype ( J:233595 )

♀N • both genes are expressed in ovaria, but ovulation, fertilization, preimplantation embryo development and hormone production are normal in conditional gain-of-function females

abnormal uterus morphology ( J:233595 )

♀ • persistent apicobasal polarity in the luminal epithelium with increased cell heights and retention of glycosylated microvilli on the apical surface

abnormal maternal decidual layer morphology ( J:233595 )

♀ • abnormal primary decidual zone (PDZ) development at 6 dpc

♀ • PDZ was absent in some implantation sites with the embryo entrapped within the intact epithelium at 6 dpc

abnormal embryo attachment ( J:233595 )

♀ • uteri either failed to show or had very weak endometrial vascular permeability at the site of blastocyst attachment at 5 dpc

♀ • unattached blastocysts were recovered from uteri at 5 dpc

♀ • defects in crypt formation

♀ • some blastocysts situated within the primary lumen

abnormal uterine-embryonic axis ( J:233595 )

♀ • inappropriate mesometrial-antimesometrial (M-AM) orientation of implantation sites at 5, 6 and 8 dpc: closer to M pole instead of at AM pole

♀ • ratio of M-AM axis length to anterior-posterior (A-P) axis length is reduced by ~25% resulting in a more spherical morphology at 8 dpc

impaired embryo implantation ( J:233595 )

♀ • uteri either failed to show or had very weak endometrial vascular permeability at the site of blastocyst attachment at 5 dpc

♀ • different sizes of implantation sites at 8 dpc

impaired spacing of implantation sites ( J:233595 )

♀ • implantation sites were often irregularly spaced at 5 and 8 dpc

twin decidual capsule ( J:233595 )

♀ • two embryos closely apposed within one implantation site

reduced female fertility ( J:233595 )

♀ • plug-positive females are either sterile or produce a small litter

♀ • high resorption rates

decreased litter size ( J:233595 )

♀ • in the few fertile mice

embryo

abnormal trophoblast giant cell proliferation ( J:233595 )

♀ • clusters of Prl3d1-positive trophoblast giant cells in implantation sites in lieu of the embryo proper at 10 dpc

abnormal embryo development ( J:233595 )

♀ • increasing numbers of resorption sites on 10 and 12 dpc

♀ • absent or substantially smaller embryos in many implantation sites from 10 dpc

abnormal placenta morphology ( J:233595 )

♀ • in surviving implantation sites at 12 dpc

♀ • disrupted placental development from 10 dpc

abnormal maternal decidual layer morphology ( J:233595 )

♀ • abnormal primary decidual zone (PDZ) development at 6 dpc

♀ • PDZ was absent in some implantation sites with the embryo entrapped within the intact epithelium at 6 dpc

decreased placental labyrinth size ( J:233595 )

♀ • Gcm1-positive syncytiotrophoblasts in the labyrinth failed to elongate, suggesting disrupted secondary branching morphogenesis of placental villi at 12 dpc

cellular

abnormal trophoblast giant cell proliferation ( J:233595 )

♀ • clusters of Prl3d1-positive trophoblast giant cells in implantation sites in lieu of the embryo proper at 10 dpc

Genotype
MGI:5780553

cn28

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-Errfi1)Jwj}/?; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:218222 )

♀ • mice exhibit normal survival with no differences in uterine/body weight ratio or uterine morphology at 2-3 months of age relative to controls

Genotype
MGI:6118935

cn29

• Allelic Composition: Pgrmc1^tm1.1Jjp/Pgrmc1^tm1.1Jjp; Pgrmc2^tm1.1Jjp/Pgrmc2⁺; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

endocrine/exocrine glands

enlarged endometrial glands ( J:247103 )

♀ • enlarged amorphic and cystic glands characteristic of aged endometrium

reproductive system

enlarged endometrial glands ( J:247103 )

♀ • enlarged amorphic and cystic glands characteristic of aged endometrium

Genotype
MGI:6118934

cn30

• Allelic Composition: Pgrmc1^tm1.1Jjp/Pgrmc1^tm1.1Jjp; Pgrmc2^tm1.1Jjp/Pgrmc2^tm1.1Jjp; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

early reproductive senescence ( J:247103 )

♀ • in female mice

reproductive system

uterus cyst ( J:247103 )

♀ • in all mice at 4 to 5 months compared with some wild-type mice at 5 to 8 months

early reproductive senescence ( J:247103 )

♀ • in female mice

abnormal endometrium morphology ( J:247103 )

♀ • breakdown of basement membrane and disruption of epithelial-stromal interface

abnormal endometrial gland morphology ( J:247103 )

♀ • vacuolated nuclei, intracellular inclusion bodies and excessive, highly convoluted plasma membrane in glandular epithelial cells

increased endometrial gland number ( J:247103 )

♀

enlarged endometrial glands ( J:247103 )

♀ • enlarged amorphic and cystic glands characteristic of aged endometrium

reduced female fertility ( J:247103 )

♀ • female mice have fewer pups per litter and fewer litters per female compared with control mice

decreased litter size ( J:247103 )

♀ • fewer pups per litter and fewer litters per female

endocrine/exocrine glands

abnormal endometrial gland morphology ( J:247103 )

♀ • vacuolated nuclei, intracellular inclusion bodies and excessive, highly convoluted plasma membrane in glandular epithelial cells

increased endometrial gland number ( J:247103 )

♀

enlarged endometrial glands ( J:247103 )

♀ • enlarged amorphic and cystic glands characteristic of aged endometrium

growth/size/body

uterus cyst ( J:247103 )

♀ • in all mice at 4 to 5 months compared with some wild-type mice at 5 to 8 months

Genotype
MGI:6118933

cn31

• Allelic Composition: Pgrmc2^tm1.1Jjp/Pgrmc2⁺; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

endocrine/exocrine glands

enlarged endometrial glands ( J:247103 )

♀ • enlarged amorphic and cystic glands characteristic of aged endometrium

reproductive system

enlarged endometrial glands ( J:247103 )

♀ • enlarged amorphic and cystic glands characteristic of aged endometrium

Genotype
MGI:6118932

cn32

• Allelic Composition: Pgrmc2^tm1.1Jjp/Pgrmc2^tm1.1Jjp; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

early reproductive senescence ( J:247103 )

♀ • 50% of female mice become infertile after the third parity

reproductive system

decreased uterine NK cell number ( J:247103 )

♀ • at 6 days of pregnancy

uterus cyst ( J:247103 )

♀ • in all mice at 4 to 5 months compared with some wild-type mice at 5 to 8 months

early reproductive senescence ( J:247103 )

♀ • 50% of female mice become infertile after the third parity

abnormal endometrium morphology ( J:247103 )

♀ • breakdown of basement membrane and disruption of epithelial-stromal interface

abnormal endometrial gland morphology ( J:247103 )

♀ • vacuolated nuclei, intracellular inclusion bodies and excessive, highly convoluted plasma membrane in glandular epithelial cells

increased endometrial gland number ( J:247103 )

♀

enlarged endometrial glands ( J:247103 )

♀ • enlarged amorphic and cystic glands characteristic of aged endometrium

reduced female fertility ( J:247103 )

♀ • despite normal ovulation, female mice have fewer pups per litter and fewer litters per female compared with control mice

♀ • however, weanling weights are normal

decreased litter size ( J:247103 )

♀ • fewer pups per litter and fewer litters per female

homeostasis/metabolism

decreased circulating progesterone level ( J:247103 )

♀ • marginally at 10.5 days of pregnancy

embryo

decreased uterine NK cell number ( J:247103 )

♀ • at 6 days of pregnancy

immune system

decreased uterine NK cell number ( J:247103 )

♀ • at 6 days of pregnancy

endocrine/exocrine glands

decreased uterine NK cell number ( J:247103 )

♀ • at 6 days of pregnancy

abnormal endometrial gland morphology ( J:247103 )

♀ • vacuolated nuclei, intracellular inclusion bodies and excessive, highly convoluted plasma membrane in glandular epithelial cells

increased endometrial gland number ( J:247103 )

♀

enlarged endometrial glands ( J:247103 )

♀ • enlarged amorphic and cystic glands characteristic of aged endometrium

hematopoietic system

decreased uterine NK cell number ( J:247103 )

♀ • at 6 days of pregnancy

growth/size/body

uterus cyst ( J:247103 )

♀ • in all mice at 4 to 5 months compared with some wild-type mice at 5 to 8 months

Genotype
MGI:6850681

cn33

• Allelic Composition: Atg16l1^{tm1c(EUCOMM)Wtsi}/Atg16l1^{tm1c(EUCOMM)Wtsi}; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

reproductive system

abnormal decidualization ( J:287978 )

♀ • after oil-induced artificial decidualization, stimulated uterine horns weigh more than unstimulated horns but remain smaller than stimulated horns of control mice

♀ • stimulated horns fail to increase expression of the decidualization markers Bmp2 and Wnt4, endometrial stromal cells maintain a fibroblast morphology instead of assuming a rounded decidual cell morphology, and LC3B-II levels are downregulated, indicating impaired endometrial decidualization

impaired embryo implantation ( J:287978 )

♀ • at 6 dpc, females have on average 2 fewer implantation sites than controls, indicating a decreased implantation rate

♀ • however, no defects in ovulation or fertilization are found at 4 dpc

reduced female fertility ( J:287978 )

♀ • when mated with wild-type males of proven fertility, females produce fewer pups than controls after their first parity

♀ • over a 6 mo-period of continuous breeding, females have significantly fewer litters, smaller litter size, and reduced fecundity relative controls

♀ • during natural mating, time to first litter (as measured by plug date to delivery date) is extended, suggesting that many females fail to get pregnant after their first mating

decreased litter size ( J:287978 )

♀ • when mated with wild-type, females produce a significantly smaller litter size than controls

embryo

abnormal decidualization ( J:287978 )

♀ • after oil-induced artificial decidualization, stimulated uterine horns weigh more than unstimulated horns but remain smaller than stimulated horns of control mice

♀ • stimulated horns fail to increase expression of the decidualization markers Bmp2 and Wnt4, endometrial stromal cells maintain a fibroblast morphology instead of assuming a rounded decidual cell morphology, and LC3B-II levels are downregulated, indicating impaired endometrial decidualization

Genotype
MGI:5052044

cn34

• Allelic Composition: Phb1^tm1.1Bwo/Phb1^tm1.1Bwo; Pgr^tm2(cre)Lyd/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

reproductive system

abnormal uterus morphology ( J:173884 )

♀

abnormal endometrium morphology ( J:173884 )

♀ • endometrium is significantly reduced although uterine structure is otherwise normal

♀ • luminal and glandular epithelial cells are present

♀ • endometrium does respond to estradiol

endometrium hypoplasia ( J:173884 )

♀

thin uterine horn ( J:173884 )

♀ • circumference of uterine horns is significantly reduced although length is normal

abnormal uterus size ( J:173884 )

♀

decreased uterus weight ( J:173884 )

♀ • uterus to body weight ratio is significantly reduced by 5 weeks of age

♀ • estradiol has little effect on uterine growth

female infertility ( J:173884 )

♀ • when Phb expression is ablated in the uterus, female mice are sterile

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:173884 )

N • serum estradiol levels are normal

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:173884 )

N • ovarian morphology is apparently normal

Genotype
MGI:6281662

cn35

• Allelic Composition: Hdac3^tm1.1Eno/Hdac3^tm1.1Eno; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6

reproductive system

reproductive system phenotype ( J:269518 )

♀N • females exhibit normal ovulation, fertilization, and ovarian histology relative to control mice

abnormal decidualization ( J:269518 )

♀ • at day 5.5 of gestation (GD 5.5), embryos are free-floating within the uterine lumen and no decidual cells are observed, unlike in control uteri

♀ • following artificially induced decidualization, the ratio of uterine weight to body weight is significantly lower than that in control mice, indicating a decidual defect; mRNA expression of decidualization marker genes Wnt4 and Bmp2 is significantly reduced in the uterus

abnormal endometrium morphology ( J:269518 )

♀ • at GD 3.5, the expression of stromal markers vimentin and COUP-TFII is significantly reduced in endometrial stromal cells

endometrium fibrosis ( J:269518 )

♀ • immunohistochemical staining showed significantly increased collagen type I protein levels in endometrial stromal cells at GD 3.5, suggesting that endometrial stroma is largely replaced by fibrous tissue

abnormal embryo attachment ( J:269518 )

♀ • at GD 5.5, embryos are free-floating within the uterine lumen, unlike in control uteri

failure of embryo implantation ( J:269518 )

♀ • no implantation sites are detected in the uterine horns at GD 5.5

abnormal uterine receptivity ( J:269518 )

♀

abnormal uterus physiology ( J:269518 )

♀ • at GD 3.5, Ki-67 staining revealed significantly altered proliferative responses in the uterine stromal and epithelial compartments: the % of Ki-67+ endometrial epithelial cells is increased whereas the % of Ki-67+ stromal cells is decreased, unlike in control uteri

♀ • expression of estrogen receptor 1 alpha (ESR1) and progesterone receptor (PGR) is significantly reduced in endometrial stromal cells at GD 3.5, indicating decreased progesterone signaling

female infertility ( J:269518 )

♀ • adult females are completely sterile primarily due to a uterine defect

embryo

abnormal decidualization ( J:269518 )

♀ • at day 5.5 of gestation (GD 5.5), embryos are free-floating within the uterine lumen and no decidual cells are observed, unlike in control uteri

♀ • following artificially induced decidualization, the ratio of uterine weight to body weight is significantly lower than that in control mice, indicating a decidual defect; mRNA expression of decidualization marker genes Wnt4 and Bmp2 is significantly reduced in the uterus

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:269518 )

♀N • at GD 3.5, females exhibit normal serum progesterone and estrogen levels relative to control mice

increased collagen level ( J:269518 )

♀ • H&E and Massons trichrome staining revealed increased collagen levels in uterine stromal cells starting at 6 weeks of age

♀ • immunohistochemical staining showed significantly increased collagen type I protein levels in endometrial stromal cells at GD 3.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometriosis		DOID:289		J:269518

Genotype
MGI:3716555

cn36

• Allelic Composition: Ncoa1^tm1Bwo/Ncoa1^tm1Bwo; Ncoa2^tm1.1Ipc/Ncoa2^tm1.1Ipc; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129S2/SvPas * 129X1/SvJ

reproductive system

abnormal decidualization ( J:117006 )

♀ • uterus fails to display any decidual response upon stimulation

embryo

abnormal decidualization ( J:117006 )

♀ • uterus fails to display any decidual response upon stimulation

Genotype
MGI:7279155

cn37

• Allelic Composition: Pgr^tm2(cre)Lyd/Pgr⁺; Cripto^tm2.2Mms/Cripto^tm2.2Mms
• Genetic Background: involves: 129/Sv * C57BL/6N * CD-1

reproductive system

abnormal endometrial gland morphology ( J:324146 )

♀ • 3.5 dpc uteri of old (7- to 8-month-old) mated females display distended endometrial glands in 6 of 7 females, unlike in aged-matched controls

endometrium inflammation ( J:324146 )

♀ • 3.5 dpc uteri of old (7- to 8-month-old) mated females show marked infiltration of immune cells into the distended lumen of uterine glands in 4 of 7 females, unlike in aged-matched controls

abnormal pregnancy ( J:324146 )

♀ • although the preimplantation period is normal, ~20% of females fail to establish pregnancy with no signs of any decidua

♀ • an additional 20% of females establish pregnancy but show full litter loss after implantation between 5.5 dpc and 8.5 dpc

♀ • however, ~60% of females establish pregnancy and show normal fertility parameters until 8.5 dpc

♀ • also, serum progesterone (P4) levels are normal in all 3 categories at 7.5 dpc

abnormal embryo attachment ( J:324146 )

♀ • uteri of 5.5 dpc mated but nonpregnant females show no signs of embryo attachment

delayed embryo implantation ( J:324146 )

♀ • in 20% of females that lose their entire litter, loss of pregnancy between 5.5 dpc and 8.5 dpc may be the result of delayed implantation

failure of embryo implantation ( J:324146 )

♀ • ~20% of females fail to establish pregnancy with no signs of any decidua, even though a mating plug and corpora lutea are observed

♀ • uteri of 5.5 dpc mated but nonpregnant females show no signs of embryo attachment/implantation

abnormal uterine environment ( J:324146 )

♀ • peri-implantation remodeling of the uterine lumen and stroma is impaired during pregnancy; however, proliferation of uterine stromal cells is normal on 4.5 dpc

♀ • expression of Notch signaling components Notch1, Notch4, and Dll4 is significantly lower in the uteri of pregnant 5.5 dpc females than in pregnant 5.5 dpc controls

♀ • in old (7- to 8-month-old) mated females, the number of viable blastocysts retrieved from the 3.5 dpc uterus is less than half of that in control females, suggesting that uterine environment is unfavorable for blastocysts survival and implantation as age progresses

abnormal decidualization ( J:324146 )

♀ • uteri of 5.5 dpc mated but nonpregnant females show no signs of decidualization initiation

♀ • following artificial induction of the decidual reaction, pseudopregnant females fail to show any signs of decidualization response in the scratched uterine horn

♀ • expression of Bmp2 and Wnt4 (both critical decidualization elements) is significantly lower in 5.5 dpc nonpregnant females than in pregnant 5.5 dpc females and controls

♀ • expression of Wnt4 is also significantly lower in pregnant 5.5 dpc females than in pregnant 5.5 dpc controls

♀ • alkaline phosphatase (ALP) activity is drastically lower in 5.5 dpc implantation sites than in controls, indicating impaired differentiation of decidual cells

abnormal luminal closure ( J:324146 )

♀ • implantations sites show incomplete luminal closure on 4.5 dpc and 7.5 dpc, unlike in controls

abnormal uterine-embryonic axis ( J:324146 )

♀ • an abnormal implantation crypt of irregular shape and an extra branch is observed on 3.5 dpc instead of the single longitudinal implantation crypt oriented along the anti-mesometrial/mesometrial (AM/M) axis of the uterus found in 3.5 dpc controls

female infertility ( J:324146 )

♀ • 7- to 8-month-old virgin females mated with wild-type fertile males fail to give birth to any pups after 2 rounds of successful mating, indicating a drastic age-associated decline in fertility

♀ • however, these old females are cyclic and ovulate normally

reduced female fertility ( J:324146 )

♀ • only 62% of 6-8-week-old virgin females mated with wild-type fertile males give birth to live pups and a slightly but statistically significant lower number of pups per litter is observed relative to controls

♀ • subcutaneous P4 supplementation on 3.5 dpc fails to improve the pregnancy rate

decreased litter size ( J:324146 )

♀ • when fertility of 6-8-week-old females is followed over a 5-month breeding trial, average number of litters per female is normal but average number of pups per litter is significantly lower than in controls

♀ • also, average number of pups per litter shows a marked decline over time, unlike in control females

embryo

abnormal decidualization ( J:324146 )

♀ • uteri of 5.5 dpc mated but nonpregnant females show no signs of decidualization initiation

♀ • following artificial induction of the decidual reaction, pseudopregnant females fail to show any signs of decidualization response in the scratched uterine horn

♀ • expression of Bmp2 and Wnt4 (both critical decidualization elements) is significantly lower in 5.5 dpc nonpregnant females than in pregnant 5.5 dpc females and controls

♀ • expression of Wnt4 is also significantly lower in pregnant 5.5 dpc females than in pregnant 5.5 dpc controls

♀ • alkaline phosphatase (ALP) activity is drastically lower in 5.5 dpc implantation sites than in controls, indicating impaired differentiation of decidual cells

endocrine/exocrine glands

abnormal endometrial gland morphology ( J:324146 )

♀ • 3.5 dpc uteri of old (7- to 8-month-old) mated females display distended endometrial glands in 6 of 7 females, unlike in aged-matched controls

immune system

endometrium inflammation ( J:324146 )

♀ • 3.5 dpc uteri of old (7- to 8-month-old) mated females show marked infiltration of immune cells into the distended lumen of uterine glands in 4 of 7 females, unlike in aged-matched controls

Genotype
MGI:5444650

cn38

• Allelic Composition: Ncoa6^tm3Jxu/Ncoa6^tm3Jxu; Pgr^tm2(cre)Lyd/Pgr⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL

reproductive system

abnormal decidualization ( J:189065 )

♀ • the decidual response is diminished

abnormal luminal closure ( J:189065 )

♀ • display intricately extended luminal and glandular epithelia that surround the curving lumens with many branches on the uterine cross-sections suggesting epithelial overgrowth

abnormal uterine receptivity ( J:189065 )

♀ • no implantation sites are found

♀ • embryos transferred into control females are able to attach to the uterus

♀ • treatment with a low dose of an estrogen receptor antagonist rescues embryo implantation

female infertility ( J:189065 )

♀ • ovulation and blastocyst formation are normal but no implantation sites are found

embryo

abnormal decidualization ( J:189065 )

♀ • the decidual response is diminished