B6;129-Chordc1tm1Mbra/Cnrm

Status

Under development - register interest

EMMA IDEM:15966
Citation informationRRID:IMSR_EM:15966 

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International strain nameB6;129-Chordc1tm1Mbra/Cnrm
Alternative namechordc1+/- (morgana +/-) C57BL/6j × 129SV
Strain typeTargeted Mutant Strains : Knock-out
Allele/Transgene symbolChordc1tm1Mbra
Gene/Transgene symbolChordc1

Information from provider

ProviderMara Brancaccio
Provider affiliationDepartment of Molecular Biotechnology and Health Sciences, University of Torino
Genetic informationThe Morgana coding gene (Chordc1) was inactivated by homologous recombination in mouse ES cells. The knock-out construct consisted of a 5′ arm (a 3.5 kb genomic fragment), a β-galactosidase gene with a neomycin resistance cassette (6 kb) and a 3′ arm (a 6.3 kb genomic fragment). ES recombinant clones lacking a 30 bp sequence including the Chordc1 ATG translation start site were identified by Southern blot analysis and injected into C57BL/6 blastocysts to generate chimeras (Ferretti R et al., Dev Cell. 2010, 18(3):486-95. doi: 10.1016/j.devcel.2009.12.020. PMID:20230755)
Phenotypic informationHomozygous:
Homozygous mutation of the Morgana coding gene (Chordc1) leads to preimplantation lethality. At 3.5 days post coitum, morphologically normal Chordc1-/⁻- embryos were observed at a Mendelian frequency, but no embryos were detectable after implantation.

Heterozygous:
Chordc1+/- (Morgana+/-) mice exhibit increased susceptibility to neoplastic transformation when treated at birth with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) and examined five months later for lung tumor formation. Morgana+/− mice showed a 2.5-fold increase in lung tumor frequency compared to their wild-type littermates subjected to the same treatment. Starting at 12 months of age, 60% of Chordc1+/- (Morgana+/- ) mice spontaneously develop a lethal myeloproliferative disorder resembling human atypical chronic myeloid leukemia (aCML), characterized by centrosome amplification and cytogenetic abnormalities in the bone marrow.
Breeding historyES recombinant clones (129Sv) have been injected into C57BL/6 blastocysts to generate chimeras. Chimeras have been mated with C57BL/6J and offspring of different chimeras were mated together.
References
  • Morgana acts as an oncosuppressor in chronic myeloid leukemia.;Di Savino Augusta, Panuzzo Cristina, Rocca Stefania, Familiari Ubaldo, Piazza Rocco, Crivellaro Sabrina, Carrà Giovanna, Ferretti Roberta, Fusella Federica, Giugliano Emilia, Camporeale Annalisa, Franco Irene, Miniscalco Barbara, Cutrin Juan Carlos, Turco Emilia, Silengo Lorenzo, Hirsch Emilio, Rege-Cambrin Giovanna, Gambacorti-Passerini Carlo, Pandolfi Pier Paolo, Papotti Mauro, Saglio Giuseppe, Tarone Guido, Morotti Alessandro, Brancaccio Mara, ;2015;Blood;125;2245-53; 25678499
  • Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication and tumorigenesis.;Ferretti Roberta, Palumbo Valeria, Di Savino Augusta, Velasco Silvia, Sbroggiò Mauro, Sportoletti Paolo, Micale Lucia, Turco Emilia, Silengo Lorenzo, Palumbo Gioacchino, Hirsch Emilio, Teruya-Feldstein Julie, Bonaccorsi Silvia, Pandolfi Pier Paolo, Gatti Maurizio, Tarone Guido, Brancaccio Mara, ;2010;Developmental cell;18;486-95; 20230755
Homozygous fertileno
Homozygous viableno
Homozygous matings requiredno
Immunocompromisedno

Information from EMMA

Archiving centreCNR, Consiglio Nazionale delle Ricerche, Monterotondo, Italy

Disease and phenotype information

IMPC phenotypes (gene matching)
  • abnormal skin morphology / IMPC
  • cataract / IMPC
  • small kidney / IMPC
  • abnormal neural tube morphology / IMPC
  • preweaning lethality, complete penetrance / IMPC
  • increased neutrophil cell number / IMPC
  • abnormal kidney morphology / IMPC
  • decreased lymphocyte cell number / IMPC
  • embryonic lethality prior to organogenesis / IMPC
  • abnormal vitreous body morphology / IMPC
  • abnormal retina morphology / IMPC

Literature references

  • Morgana acts as an oncosuppressor in chronic myeloid leukemia.;Di Savino Augusta, Panuzzo Cristina, Rocca Stefania, Familiari Ubaldo, Piazza Rocco, Crivellaro Sabrina, Carrà Giovanna, Ferretti Roberta, Fusella Federica, Giugliano Emilia, Camporeale Annalisa, Franco Irene, Miniscalco Barbara, Cutrin Juan Carlos, Turco Emilia, Silengo Lorenzo, Hirsch Emilio, Rege-Cambrin Giovanna, Gambacorti-Passerini Carlo, Pandolfi Pier Paolo, Papotti Mauro, Saglio Giuseppe, Tarone Guido, Morotti Alessandro, Brancaccio Mara, ;2015;Blood;125;2245-53; 25678499
  • Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication and tumorigenesis.;Ferretti Roberta, Palumbo Valeria, Di Savino Augusta, Velasco Silvia, Sbroggiò Mauro, Sportoletti Paolo, Micale Lucia, Turco Emilia, Silengo Lorenzo, Palumbo Gioacchino, Hirsch Emilio, Teruya-Feldstein Julie, Bonaccorsi Silvia, Pandolfi Pier Paolo, Gatti Maurizio, Tarone Guido, Brancaccio Mara, ;2010;Developmental cell;18;486-95; 20230755

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