Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names C.129S1-Ightm1Janz/J    (Changed: 17-MAY-10 ) Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Heterozygote         (Female x Male)   01-FEB-10 Species laboratory mouse   Donating Investigator Siegfried Janz,   University of Iowa

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.

Control Information

	Control
	Wild-type from the colony
	001026 BALB/cByJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Igh

012642	B6.129P2(C)-Ightm2Cgn/J
007776	B6.129P2-Ightm2Mnz/J
007594	B6.129P2-Ptrpca Ightm1Mnz/J
001317	B6.Cg-Igha Thy1a Gpi1a/J
011074	C.129P2(B6)-Igktm1Rsky Ightm2Rsky/PldJ
012235	C.129P2(B6)-Igktm2Rsky Ightm2Rsky/J
001109	C.AL-Igho/SmnJ
001107	C.BKa-Ighb/IcrSmnJ
004126	C.Cg-Cd19tm1(cre)Cgn Ighb/J
007775	CBy.129P2(B6)-Ightm1Mnz/J

View Strains carrying other alleles of Igh     (10 strains)

Strains carrying other alleles of Myc

007693	B6(Cg)-Myctm37Mnz/J
007692	B6(Cg)-Myctm39Mnz/J
002728	B6.Cg-Tg(IghMyc)22Bri/J
011001	B6;129S4-Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch/J
008341	C.129S1-Ighatm1(Myc)Janz/J
002677	FVB.Cg-Tg(WapMyc)212Bri/J
011004	STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm3(tetO-Pou5f1,-Sox2,-Klf4,-Myc)Jae/J
011011	STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm4(tetO-Pou5f1,-Sox2,-Klf4,-Myc)Jae/J
011013	STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm5(tetO-Pou5f1,-Klf4,-Myc)Jae/J
019075	STOCK Myctm1.1Dlev/J
012279	STOCK Tg(Piwil1)2Ghan/J
012281	STOCK Tg(Piwil4)2Ghan/J

View Strains carrying other alleles of Myc     (12 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Burkitt Lymphoma; BL

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Igh^tm1(Myc)Janz/Igh⁺

        involves: 129X1/SvJ * C57BL/6

• tumorigenesis
• altered tumor morphology
  • tumors are more differentiated than tumors from Igh^tm1(Myc)Janz Tg(Emu-FGFR3)A5Wmk or Tg(Emu-FGFR3)D3Wmk heterozygotes   (MGI Ref ID J:160845)
• increased tumor incidence
  • tumor incidence was 68% at 21 months of age   (MGI Ref ID J:96785)
  • 75% of mice developed tumors at a median age of 281 days unlike wild-type mice   (MGI Ref ID J:160845)
• • B cell derived lymphoma   (MGI Ref ID J:160845)
    • most prevalent tumors were lymphoblastic B cell lymphomas with a Burkitt-like 'starry sky' morphology due to tingible body macrophages   (MGI Ref ID J:96785)
    • 1/4 of lymphomas were diffuse large B cell lymphomas   (MGI Ref ID J:96785)
    • lymphoblastic B-cell lymphomas contain clonal cytogenetic aberrations   (MGI Ref ID J:96785)
  • increased plasmacytoma incidence
    • 1/5 of lymphomas were CD19⁺CD138⁺ plasmacytomas that exhibited varying degrees of differentiation, including plasmablastic, anaplastic, and plasmacytic variants   (MGI Ref ID J:96785)
    • 25% of tumor exhibit plasmacytoid differentiation   (MGI Ref ID J:160845)
• immune system phenotype
• enlarged lymph nodes
  • lymph nodes were enlarged in 4- to 6-month tumor-free mice because of progressive, follicular hyperplasia indicative of B cell accumulation   (MGI Ref ID J:96785)
• enlarged spleen
  • spleen was enlarged in 4- to 6-month old tumor-free mice because of progressive, follicular hyperplasia indicative of B cell accumulation   (MGI Ref ID J:96785)
• increased B cell apoptosis
  • elevated apoptosis in B cells of 4- to 6-month old tumor-free mutants   (MGI Ref ID J:96785)
• increased B cell proliferation
  • B cells proliferated, on average, 3.8 times faster than controls and showed a 3.5-fold increase in the number of cells in S phase of the cell cycle in 4- to 6-month old, tumor-free mutants   (MGI Ref ID J:96785)
  • B splenocytes proliferated more vigorously than controls after stimulation with LPS   (MGI Ref ID J:96785)
• lymphoid hyperplasia
  • observed in 4- to 6-month old tumor-free mutants   (MGI Ref ID J:96785)
• hematopoietic system phenotype
• enlarged spleen
  • spleen was enlarged in 4- to 6-month old tumor-free mice because of progressive, follicular hyperplasia indicative of B cell accumulation   (MGI Ref ID J:96785)
• increased B cell proliferation
  • B cells proliferated, on average, 3.8 times faster than controls and showed a 3.5-fold increase in the number of cells in S phase of the cell cycle in 4- to 6-month old, tumor-free mutants   (MGI Ref ID J:96785)
  • B splenocytes proliferated more vigorously than controls after stimulation with LPS   (MGI Ref ID J:96785)
• cellular phenotype
• increased B cell apoptosis
  • elevated apoptosis in B cells of 4- to 6-month old tumor-free mutants   (MGI Ref ID J:96785)
• increased B cell proliferation
  • B cells proliferated, on average, 3.8 times faster than controls and showed a 3.5-fold increase in the number of cells in S phase of the cell cycle in 4- to 6-month old, tumor-free mutants   (MGI Ref ID J:96785)
  • B splenocytes proliferated more vigorously than controls after stimulation with LPS   (MGI Ref ID J:96785)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cancer Research
Increased Tumor Incidence
      Lymphomas
      Lymphomas: B cell lymphomas

Research Tools
Immunology and Inflammation Research
      B cell lymphomas

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ightm1(Myc)Janz
Allele Name		targeted mutation 1, Siegfried Janz
Allele Type		Targeted (knock-in)
Common Name(s)		iMycEmu;
Mutation Made By		Siegfried Janz,   University of Iowa
Expressed Gene		Myc, myelocytomatosis oncogene, mouse, laboratory
Gene Symbol and Name		Igh, immunoglobulin heavy chain complex
Chromosome		12
Molecular Note		A His6-tagged Myc cDNA was inserted head to head into the locus 5' of the intronic enhancer Emu. 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. [MGI Ref ID J:96785]

Genotyping

Genotyping Information

Genotyping Protocols

Igh^tm1Janz, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Park SS; Kim JS; Tessarollo L; Owens JD; Peng L; Han SS; Tae Chung S; Torrey TA; Cheung WC; Polakiewicz RD; McNeil N; Ried T; Mushinski JF; Morse HC 3rd; Janz S. 2005. Insertion of c-Myc into Igh induces B-cell and plasma-cell neoplasms in mice. Cancer Res 65(4):1306-15. [PubMed: 15735016]  [MGI Ref ID J:96785]

Additional References

Igh^tm1(Myc)Janz related

Bommert KS; Effenberger M; Leich E; Kuspert M; Murphy D; Langer C; Moll R; Janz S; Mottok A; Weissbach S; Rosenwald A; Bargou R; Bommert K. 2013. The feed-forward loop between YB-1 and MYC is essential for multiple myeloma cell survival. Leukemia 27(2):441-50. [PubMed: 22772059]  [MGI Ref ID J:193665]

Kim J; Han S; Park S; McNeil N; Janz S. 2006. Plasma cell tumour progression in iMyc(Emicro) gene-insertion mice. J Pathol 209(1):44-55. [PubMed: 16482495]  [MGI Ref ID J:107719]

Park ES; Shaughnessy JD Jr; Gupta S; Wang H; Lee JS; Woo HG; Zhan F; Owens JD Jr; Potter M; Janz S; Mushinski JF. 2007. Gene expression profiling reveals different pathways related to Abl and other genes that cooperate with c-Myc in a model of plasma cell neoplasia. BMC Genomics 8:302. [PubMed: 17764563]  [MGI Ref ID J:128718]

Park SS; Shaffer AL; Kim JS; duBois W; Potter M; Staudt LM; Janz S. 2005. Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice. Cancer Res 65(17):7644-52. [PubMed: 16140930]  [MGI Ref ID J:102146]

Rutsch S; Neppalli VT; Shin DM; Dubois W; Morse HC 3rd; Goldschmidt H; Janz S. 2010. IL-6 and MYC collaborate in plasma cell tumor formation in mice. Blood 115(9):1746-54. [PubMed: 20018915]  [MGI Ref ID J:157726]

Wang YV; Leblanc M; Wade M; Jochemsen AG; Wahl GM. 2009. Increased radioresistance and accelerated B cell lymphomas in mice with Mdmx mutations that prevent modifications by DNA-damage-activated kinases. Cancer Cell 16(1):33-43. [PubMed: 19573810]  [MGI Ref ID J:150341]

Zhu D; Qi CF; Morse HC 3rd; Janz S; Stevenson FK. 2005. Deregulated expression of the Myc cellular oncogene drives development of mouse 'Burkitt-like' lymphomas from naive B cells. Blood 105(5):2135-7. [PubMed: 15522957]  [MGI Ref ID J:95904]

Zingone A; Cultraro CM; Shin DM; Bean CM; Morse HC 3rd; Janz S; Kuehl WM. 2010. Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate development of B-cell lineage neoplasms. Leukemia 24(6):1171-8. [PubMed: 20393505]  [MGI Ref ID J:160845]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Heterozygote x Heterozygote         (Female x Male)   01-FEB-10

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	001026 BALB/cByJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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