C57BL/6J-Tg(Vav1-MYC)10Sco/J

Stock number: 037904
Product name: VavP-MYC10
Research areas: Apoptosis Research, Cancer Research, Cell Biology Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

VavP-MYC10 transgenic mice express MYC cDNA, encompassing the coding region but lacking any 5' or 3' untranslated sequence, under control of the endogenous vav 1 oncogene enhancer/promoter (Vav1). These mice may be useful for studying overexpression of MYC in cancer biology, cell proliferation, differentiation, DNA damage response and apoptosis.

Detailed description

Myelocytomatosis gene (MYC) is a basic helix-loop-helix-leucine zipper transcription factor regulating numerous genes involved in cell growth, proliferation, metabolism, DNA damage response and apoptosis. MYC protein binds DNA at CACGTG E-boxes (and variants) as a heterodimer with MAX (MYC Associated Factor X). Overexpression of MYC is a driver of many types of cancer, such as human Burkitt’s lymphomas and mouse plasmacytomas.

VavP-MYC10 mice express a transgene encoding a full-length human MYC cDNA driven by enhancer/promoter of the vav 1 gene (Vav1). Transgene expression is evident in both lymphoid (T and B) and myeloid but highest in thymic T cells.

The donating laboratory distinguishes homozygous from hemizygous by platelet counts: homozygous have <650x10⁹cells/L whereas hemizygous and non-carrier mice have >1000x10⁹cells/L. While Smith et al. Blood (2006) describes hemizygous VavP-MYC10 as having 7 copies of the transgene, the donating laboratory reports more current technologies estimate the VavP-MYC10 line to carry 10 copies of the transgene (2023). The transgene insertion site(s) and configuration are not known.

Tumor progression and phenotype vary with the level of MYC expression. Homozygous VavP-MYC10 mice have thymic T lymphoma as the major cause of morbidity, although myeloid tumor cells are also often present. Hemizygous VavP-MYC10 mice present with a mixture of T lymphomas and myeloid tumors. The donating laboratory originally reported homozygotes having a median survival of ~116 days, whereas hemizygotes have a median survival of ~276 days (Campbell et al. Cell Death Diff (2017)). Importantly, they have determined a slight increase in lifespan over time with the homozygous mice showing median survival of ~134 days, potentially due to a lower expression of the transgene (Nguyen et al. Cell Death Diff (2023)).

Hemizygous females are fertile, and both homozygous and hemizygous males are fertile. The donating laboratory has been successful in mating hemizygous females to homozygous males, however they report the Mendelian ratio is lower than expected for homozygous mice (~34%) from these matings. Homozygous females are not used as breeders due to the tumor phenotype.

These VavP-MYC10 transgenic mice may be useful for studying the impact of MYC overexpression in hemopoietic biology and pathogenesis.

Development

The VavP-MYC10 transgene was generated using human MYC cDNA, encompassing the coding region but lacking any 5' or 3' untranslated sequence (Smith et al. Blood (2006)).Transgene expression is directed by the vav 1 oncogene enhancer/promoter vector (Vav1), an intron sequence from the SRα expression vector, and the SV40 late region polyadenylation signal (Ogilvy et al. Blood (1999)). Purified linearized DNA was microinjected into the pronuclei of fertilized C57BL/6J oocytes. Founder line 10 was established and maintained on a C57BL/6J background. At some point, the donating laboratory crossed these VavP-MYC10 transgenic mice to a Rag1-Cre line (MGI:3584018); donor males provided to The Jackson Laboratory were wildtype for the Rag1-Cre allele. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.

Allele

Symbol: Tg(Vav1-MYC)10Sco
Name: transgene insertion 10, Suzanne Cory
MGI accession ID: MGI:7344345
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: MYC10
Marker symbol: Tg(Vav1-MYC)10Sco
Marker name: transgene insertion 10, Suzanne Cory
Chromosome: UN
Strain of origin: C57BL/6J
Molecular note: A human MYC cDNA, encompassing the coding region butlacking any 5' or 3' untranslated sequence is expressed under the control of a mouse cloned into the Vav enhancer/promoter. Three lines were generated from this construct.