C.129S1-Igh^tm1(Myc)Janz/J

Stock number: 008332
Research areas: Cancer Research, Research Tools

Description

These mutant mice carry a His₆-tagged myelocytomatosis oncogene (Myc) gene (cDNA) sequence inserted in the endogenous immunoglobulin heavy chain complex (Igh) locus, which mimics the human endemic Burkitt lymphoma t(8;14)(q24;q32) translocation and mouse plasmacytoma T(12;15) translocation. This mutant mouse strain may be useful in studies of Burkitt Lymphoma and plasma cell and B-cell neoplasia.

Detailed description

These mutant mice carry a His₆-tagged Myc gene (cDNA) sequence inserted in the endogenous immunoglobulin heavy chain complex (Igh) locus, which mimics the human endemic Burkitt lymphoma t(8;14)(q24;q32) translocation and mouse plasmacytoma T(12;15) translocation. The His₆-tagged Myc is overexpressed in B-cells throughout B-cell development, as detected by FACS analysis. Tumor-free heterozygotes, 4 to 6 months of age, on a mixed B6;129X1 background, exhibit increased B-cell proliferation and apoptosis and have enlarged lymph nodes and spleen due to follicular hyperplasia. 68% of mutant mice between 6 and 21 months of age develop mature B-cell tumors that are IgM and BCL6 positive. Approximately half of the tumors detected are lymphoblastic B-cell lymphomas that are Burkitt-like in appearance and one fifth as plasmacytomas. The plasmacytomas occur in gut-associated lymphoid tissue (GALT), especially in the mesenteric lymph node and Peyer's patches. Mice that are homozygous for the targeted mutation are viable and fertile. This mutant mouse strain may be useful in studies of Burkitt Lymphoma and B-cell and plasma cell neoplasia.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing a floxed neo selection cassette, His₆ (an artificial histidine tag) and sequence encoding the mouse Myc gene was inserted 5' to the E-mu intronic enhancer of the Igh locus.

The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

The resulting chimeric animals were crossed to transgenic Cre recombinase expressing mice to remove the neo selection cassette. The mice were then backcrossed to BALB/cAnPt for 13 generations.

Allele

Symbol: Igh^tm1(Myc)Janz
Name: targeted mutation 1, Siegfried Janz
MGI accession ID: MGI:3574400
Generation method: Targeted
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Igh
Marker name: immunoglobulin heavy chain complex
Chromosome: 12
Strain of origin: Not Specified
Expressed genes: Myc,myelocytomatosis oncogene,mouse, laboratory
Molecular note: A construct consisting of a 1.5 kb segment of genomic 5' flanking sequence from the mouse Myc gene with the P1/P2 promoters, the first noncoding exon, a mouse Myc intron-less cDNA clone with an in-frame 6x histidine tag sequence on the 3' end, a short segment of the 3' UTR including the major polyadenylation signal, and a loxP site flanked neomycin resistance gene cassette was inserted in opposite transcriptional orientation into into the locus 5' of the intronic enhancer Emu. The neo cassette was removed through subsequent cre-mediated recombination. This insertion of Myc mimics both the human t(8;14)(q24;q32) translocation that results in the activation of MYC in human endemic Burkitt lymphomas and the homologous mouse T(12;15) translocation that deregulates Myc in mouse plasmacytomas.