MGI phenotypes (allele matching)
- embryonic lethality during organogenesis, complete penetrance / MGI
B6.129-Krastm1Bbd/Cnbc
| Status | Available to order |
| EMMA ID | EM:05945 |
| International strain name | B6.129-Krastm1Bbd/Cnbc |
| Alternative name | Kras |
| Strain type | Targeted Mutant Strains : Conditional mutation |
| Allele/Transgene symbol | Krastm1Bbd |
| Gene/Transgene symbol | Kras |
Information from provider
| Provider | Mariano Barbacid |
| Provider affiliation | Molecular Oncology, Centro Nacional de Investigaciones Oncologicas |
| Genetic information | In one homologous recombination event an IRES Beta-geo cassette was inserted into the 3' untranslated region and in a second homologous recombination event a mutation changing codon 12 in exon 1 from glycine to valine was inserted along with a floxed transcriptional stop sequence and a PGK-Hygro cassette. This resulted in bicistronic cre recombination-dependent expression of the oncogenic KrasG12V allele and the geo marker. |
| Phenotypic information | In heterozygosis, before cre-mediated recombination, there is no obvious phenotype but the mutation is embryonic lethal in homozygosis due to the lack of Kras expression. After germ line cre-mediated recombination the excised allele is embryonic lethal in heterozygosis. If the level of recombination is low in the embryo, even if it is ubiquitous (small percentage of cells recombined) the mice that are born develop spontaneous lung tumors. |
| Breeding history | Chimeras were crossed with C57BL/6J females for germ line transmission analysis. Line was maintained in heterozygosis by crossing heterozygous mice with C57BL/6J animals. More than 16 generations of crosses with C57BL/6J mice. |
| References |
|
| Homozygous fertile | no |
| Homozygous viable | no |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | CNB-CSIC, Centro Nacional de Biotecnologia, Madrid, Spain |
| Animals used for archiving | heterozygous C57BL/6J |
Disease and phenotype information
MGI allele-associated human disease models
Orphanet associated rare diseases, based on orthologous gene matching
- RAS-associated autoimmune leukoproliferative disease / Orphanet_268114
- Linear nevus sebaceus syndrome / Orphanet_2612
- Juvenile myelomonocytic leukemia / Orphanet_86834
- Toriello-Lacassie-Droste syndrome / Orphanet_3339
- Pilomyxoid astrocytoma / Orphanet_251615
- Differentiated thyroid carcinoma / Orphanet_146
- Cardiofaciocutaneous syndrome / Orphanet_1340
- Noonan syndrome / Orphanet_648
MGI phenotypes (gene matching)
- abnormal ear position / MGI
- increased leukocyte cell number / MGI
- increased neutrophil cell number / MGI
- abnormal systemic arterial blood pressure / MGI
- hypertension / MGI
- extramedullary hematopoiesis / MGI
- abnormal heart morphology / MGI
- enlarged heart / MGI
- heart hyperplasia / MGI
- thin ventricular wall / MGI
- cellular necrosis / MGI
- increased cell proliferation / MGI
- abnormal cranium morphology / MGI
- increased cranium width / MGI
- flattened snout / MGI
- liver hypoplasia / MGI
- small liver / MGI
- pale liver / MGI
- enlarged spleen / MGI
- abnormal brain development / MGI
- decreased body length / MGI
- decreased body size / MGI
- ocular hypertelorism / MGI
- anemia / MGI
- decreased embryo size / MGI
- pericardial edema / MGI
- increased papilloma incidence / MGI
- increased tumor incidence / MGI
- increased T cell derived lymphoma incidence / MGI
- increased lung adenocarcinoma incidence / MGI
- increased sarcoma incidence / MGI
- increased carcinoma incidence / MGI
- increased lung adenoma incidence / MGI
- increased skin papilloma incidence / MGI
- premature death / MGI
- abnormal definitive hematopoiesis / MGI
- abnormal kidney morphology / MGI
- no abnormal phenotype detected / MGI
- small heart / MGI
- abnormal bronchus morphology / MGI
- abnormal hematopoietic system morphology/development / MGI
- increased basophil cell number / MGI
- thin myocardium / MGI
- dilated cardiomyopathy / MGI
- no phenotypic analysis / MGI
- cardiac fibrosis / MGI
- thrombocytopenia / MGI
- increased neuron apoptosis / MGI
- increased cardiac output / MGI
- abnormal fetal cardiomyocyte proliferation / MGI
- increased hemangiosarcoma incidence / MGI
- pallor / MGI
- abnormal facial morphology / MGI
- embryonic growth retardation / MGI
- fetal growth retardation / MGI
- increased squamous cell carcinoma incidence / MGI
- abnormal myocardial fiber physiology / MGI
- abnormal embryonic neuroepithelium morphology / MGI
- enlarged myocardial fiber / MGI
- increased hematopoietic stem cell number / MGI
- abnormal large intestine crypts of Lieberkuhn morphology / MGI
- increased eosinophil cell number / MGI
- decreased cardiac muscle contractility / MGI
- liver/biliary system phenotype / MGI
- hematopoietic system phenotype / MGI
- increased cardiac muscle contractility / MGI
- increased apoptosis / MGI
- increased systemic arterial diastolic blood pressure / MGI
- increased systemic arterial systolic blood pressure / MGI
- increased myocardial fiber number / MGI
- abnormal common myeloid progenitor cell morphology / MGI
- increased lung tumor incidence / MGI
- decreased CD8-positive, alpha-beta T cell number / MGI
- abnormal common lymphocyte progenitor cell morphology / MGI
- slow postnatal weight gain / MGI
- abnormal bone marrow cell physiology / MGI
- spleen vascular congestion / MGI
- decreased lung tumor incidence / MGI
- increased mesothelioma incidence / MGI
- increased fibrosarcoma incidence / MGI
- thick aortic valve / MGI
- perinatal lethality, complete penetrance / MGI
- perinatal lethality, incomplete penetrance / MGI
- prenatal lethality, complete penetrance / MGI
- embryonic lethality, complete penetrance / MGI
- embryonic lethality during organogenesis, complete penetrance / MGI
- increased cranium height / MGI
- decreased cranium length / MGI
- increased lymphoma incidence / MGI
- triangular face / MGI
- increased embryonic neuroepithelium apoptosis / MGI
- increased myeloid cell number / MGI
- increased granulocyte monocyte progenitor cell number / MGI
Literature references
- A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.;Puyol Marta, Martín Alberto, Dubus Pierre, Mulero Francisca, Pizcueta Pilar, Khan Gulfaraz, Guerra Carmen, Santamaría David, Barbacid Mariano, ;2010;Cancer cell;18;63-73; 20609353
- Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context.;Guerra Carmen, Mijimolle Nieves, Dhawahir Alma, Dubus Pierre, Barradas Marta, Serrano Manuel, Campuzano Victoria, Barbacid Mariano, ;2003;Cancer cell;4;111-20; 12957286
- Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo.;Sansom Owen J, Meniel Valerie, Wilkins Julie A, Cole Alicia M, Oien Karin A, Marsh Victoria, Jamieson Thomas J, Guerra Carmen, Ashton Gabrielle H, Barbacid Mariano, Clarke Alan R, ;2006;Proceedings of the National Academy of Sciences of the United States of America;103;14122-7; 16959882
- Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice.;Guerra Carmen, Schuhmacher Alberto J, Cañamero Marta, Grippo Paul J, Verdaguer Lena, Pérez-Gallego Lucía, Dubus Pierre, Sandgren Eric P, Barbacid Mariano, ;2007;Cancer cell;11;291-302; 17349585
- c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma.;Blasco Rafael B, Francoz Sarah, Santamaría David, Cañamero Marta, Dubus Pierre, Charron Jean, Baccarini Manuela, Barbacid Mariano, ;2011;Cancer cell;19;652-63; 21514245
- Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence.;Guerra Carmen, Collado Manuel, Navas Carolina, Schuhmacher Alberto J, Hernández-Porras Isabel, Cañamero Marta, Rodriguez-Justo Manuel, Serrano Manuel, Barbacid Mariano, ;2011;Cancer cell;19;728-39; 21665147