Table 3.

Key information and opinions in recent OC GEMMs research

Targeted genes	Targeting technology	Histotype	Original findings and opinions	Reference
Brca1, Tp53, Pten, Lkb1	CRISPR-Cas9	HGSOC	1). Quadruple deletion of Brca1, Tp53, Pten, and Lkb1 resulted in ovarian surface papillary tumors 4 months post-TAM. 2). Within 6 months post-TAM, widespread peritoneal metastasis formed in the Lkb1 deletion cohort, and some mice generated ascites by 7 months post-TAM. 3). Between 6 and 14 m post-TAM, the incidence of peritoneal metastasis was 96% and the incidence of ascites was 74% in the Lkb1 deletion cohort.	Teng, Katie et al. [159]
Trp53, Pten, Rb1, Cdh1	Amhr2 promoter driven Cre	LGSOC, HGSOC	1). Triple deletion of Trp53, Pten, Rb1 initiated OC development in OSE cells. 2). Additional Cdh1 ablation promoted tumor dissemination and ascites formation.	Shi, Mingxin et al [160].
Rb1, Brca1, Trp53 and/or Nf1	Ovgp1-TAM promotor driven Cre	HGSOC, MMMT	1). FTE-specific inactivation of Brca1, Trp53, Rb1, and Nf1 resulted in STICs that progressed to HGSOC, with widespread metastases in some cases. 2). Brca1, Trp53 and Pten inactivation in the oviduct resulted in STICs and HGSOCs and was associated with diffuse epithelial hyperplasia and mucinous metaplasia. 3). Tumour initiation and/or progression in mice lacking conditional Pten alleles probably require the acquisition of additional defects.	Zhai, Yali et al. [161]
Pten, Apc	Ovgp1-TAM promotor driven Cre, AdCre	EMC	1). Oviductal epithelial hyperplasia and atypia formed ~ 1 month post-TAM. 2). Well-formed oviductal EMC-like tumors formed 9–12 weeks post-TAM. 3). 10 of 15 mice had extensive OC, 4 with omentum metastases; 1 with lung metastases.	Wu, Rong et al. [162]
Arid1a, Pten;Apc	AdCre	EMC	1). Arid1a inactivation enhanced epithelial differentiation in a murine model of EMC. 2). Arid1a inactivation resulted in prolonged survival in the Apc/Pten-deficient EMC model.	Zhai, Yali et al. [163]
Pten, Kras, Trp53	Amhr2 promoter driven Cre	MOC, LGSOC, SOC	1). Trp53R172H mutation promoted EOC but differently contribute to the disease in the presence or absence of the wild-type TP53 allele. 2). Ovarian tumors homozygous for Trp53R172H mutation were undifferentiated and highly metastatic, exhibited minimal TP53 transactivation activity, and expressed genes with potential regulatory functions in EOC development.	Ren, Yi A et al. [164]
Apc	Pgr promotor driven Cre	EMC	1). In 87.2% of PgrCre/+; Apcex15lox/lox mice, lesions were found in the epithelium of the distal oviduct and fimbriae. 2). In 16.3% of mice, endometrioid cysts were detected. 3). In 27.9% of mice, endometrioid ovarian tumors developed.	van der Horst, Paul H et al. [165]
Trp53, Brca1, Brca2, Pten	Pax8-TET promotor driven Cre	HGSOC	1). Deletion of Brca1 or Brca2, Tp53, and Pten in FTE resulted in STIC lesions, HGSOC, and the progression to advanced stage disease with metastases. 2). GEMM tumor showed human HGSOC biomarkers and genomically correlated with TCGA data.	Perets, Ruth et al. [166]
Trp53;Rb;Brca1;Brca2	AdCre	HGSOC	1). Inactivation of RB induced surface epithelial proliferation with progression to stage I carcinoma. 2). Additional biallelic inactivation and/or missense p53 mutation in the presence or absence of Brca1/2 caused progression to stage IV disease.	Szabova, Ludmila et al. [167]
Dicer1, Pten	Amhr2 promoter driven Cre	HGSOC	1). Dicer-Pten double-knockout resulted in aggressive primary fallopian tube tumors with ascites. 2). Fallopian tube removal at early age prevented tumor formation, confirming the FTE as tumor origin.	Kim, Jaeyeon et al. [168]
Pten, Pik3ca	AdCre	SOC; GCT	1). Pik3ca mutation requires a second hit to initiate tumorigenesis in the ovary. 2). Pik3caH1047R or Pten deletion in the ovary induced serous papillary hyperplasia and cooperated to induce SOC or GCT.	Kinross, Kathryn M et al. [169]
Pten, Kras	Amhr2 promoter driven Cre	LGSOC	1). Mutant mice developed LGSOC at an early age and with 100% penetrance. 2). KRAS is a key driver of OSE transformation.	Mullany, L K et al. [170]
Trp53, Brca1, c-Myc	Retrovirals-depended Cre	SOC	1). Myc could induce malignant transformation in Brca1 and p53 deficient cells but was not sufficient for the transformation of cells deficient for either Brca1 or p53.	Xing, Deyin et al. [171]
Pten, K-ras	AdCre	EMC	1). GEMMs showed endometriosis-like lesions within the OSE but no invasive ovarian tumors up to 10 months post-infection. 2). All GEMMs developed invasive EMC as early as 7 weeks post-infection	Dinulescu, Daniela M et al. [172]
Trp53, Rb1	AdCre	EOC	1). Dual inactivation of p53 and Rb1 is sufficient for reproducible induction of ovarian epithelial carcinogenesis in mice homozygous for conditional gene alleles. 2). Ovarian neoplasms spread intraperitoneally with ascites, and metastasize to the contralateral ovary, the lung, and the liver.	Flesken-Nikitin, Andrea et al. [173]
Trp53, c-Myc, K-ras, Akt	Retroviral gene delivery	NI	1). Addition of any two of the oncogenes c-myc, K-ras, and Akt were sufficient to induce maliganant transformation in ovarian cells deficient for p53, 2). The induced ovarian tumors in mice resembled human ovarian carcinomas in their rapid progression and intraperitoneal metastatic spread.	Orsulic, Sandra et al. [174]

HGSOC High-grade serous ovarian carcinoma, LGSOC Low-grade serous ovarian carcinoma, MMMT Malignant Müllerian mixed tumor, EMC Endometrioid carcinoma, MOC Mucinous carcinoma, SOC Serous ovarian cancer, GCT Granulosa cell tumors, EOC Epithelial ovarian cancer, TAM Tamoxifen, TET Tetracycline, STICs Serous tubal intraepithelial carcinomas, FTE fallopian tube epithelium, OSE Ovarian surface epithelium, NI Not informed