STOCK Gt(ROSA)26Sortm1.1(GSDMB_i2,-EGFP)Gmbu/Cnbc
Status | Available to order |
EMMA ID | EM:13206 |
International strain name | STOCK Gt(ROSA)26Sortm1.1(GSDMB_i2,-EGFP)Gmbu/Cnbc |
Alternative name | R26-GB2 |
Strain type | Targeted Mutant Strains : Knock-in |
Allele/Transgene symbol | Gt(ROSA)26Sortm1.1(GSDMB_i2, -EGFP)Gmbu |
Gene/Transgene symbol | Gt(ROSA)26Sor |
Information from provider
Provider | Gema Moreno-Bueno |
Provider affiliation | Biochemistry, Autonomous University of Madrid (UAM) |
Genetic information | Knock-in (KI) model ubiquitously expressing the human GSDMB isoform 2 transcript “GB2” (NM_018530.2) fused with the HA-tag sequence and the Green Fluorescent Protein (GFP) gene within the ROSA26 (R26) endogenous locus. This line was originated by crossing the conditional strain R26-STOP-GB2 (EMMA ID:13205) with the B6.FVB-Tg (EIIa-Cre)C5379Lmgd/J strain. Ubiquitous cre-mediated recombination produced the deletion of the neo-STOP cassette, thus permitting the transcriptional expression (regulated by R26 promoter) of the bicistronic mRNA GSDMB2-HA-IRES-GFP in the whole body of the animal. |
Phenotypic information | Homozygous:Mice express ubiquitously the human GSDMB2 protein (n=16 organs/tissues tested by western blot). Immunohistochemical analyses demonstrated that GSDMB2 shows different nuclear and/or cytoplasmic localization in specific tissues/cell types from healthy organs and tumors. These data suggest that this protein may have distinct biological effects depending on the cellular context or microenvironment. We performed a comprehensive histopathological analysis in multiple tissues from 75 male and female mice (homozygous and heterozygous) up to 18 months of age. Homozygous mutant animals frequently (26%) develop spontaneous lung carcinomas from 1 year of age, but the frequency and the histology of these tumors are not statistically different compared to the WT littermates. Interestingly, we observed that 17% WT mice developed macroscopic gastric carcinomas, but none of mutant mice did, suggesting a potential reduction of gastric carcinogenesis in GSDMB2-positive mice that requires further study. Other types of spontaneous cancers (breast, liver carcinomas and lymphomas) were seldom (less than 5%) observed in mutant or WT animals. Additionally, our comprehensive analysis of multiple tissues detected infrequent pathological features in other organs (e.g. lung atelectasis and emphysema, liver steatosis). Heterozygous:Heterozygous mice exhibit similar phenotypic features than homozygous mice, but the frequency of spontaneous lung carcinomas (52%) is higher in heterozygous animals. |
Breeding history | This line was originated by crossing the conditional strain R26-STOP-GB2 (EMMA ID:13205) with the B6.FVB-Tg (EIIa-Cre)C5379Lmgd/J strain. After validating the ubiquitous expression of GSDMB2-HA, heterozygous GB2/cre+ animals were crossed to remove the cre recombinase and to obtain a line expressing germline GSDMB2-HA-GFP in all tissues. The resulting mouse model, named R26-GB2, was crossed two times with the FVB/NCrl strain. Currently, homozygous animals have been crossed (sibling matings) for additional 7 generations. Thus, the model has mixed background that is enriched in the FVB genetic makeup (total 3 backcrosses with this strain). |
References |
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Homozygous fertile | yes |
Homozygous viable | yes |
Homozygous matings required | yes |
Immunocompromised | no |
Information from EMMA
Archiving centre | CNB-CSIC, Centro Nacional de Biotecnologia, Madrid, Spain |
Animals used for archiving | homozygous FVB/N, homozygous FVB/N |
Stage of embryos | 2-cell |
Literature references
- Gasdermin-B Pro-Tumor Function in Novel Knock-in Mouse Models Depends on the in vivo Biological Context.;Sarrio David, Rojo-Sebastián Alejandro, Teijo Ana, Pérez-López María, Díaz-Martín Eva, Martínez Lidia, Morales Saleta, García-Sanz Pablo, Palacios José, Moreno-Bueno Gema, ;2022;Frontiers in cell and developmental biology;10;813929; 35281099
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