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-Igh-2tm1(Myc)Janz/J    (Changed: 02-NOV-11 ) Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?pN1 Generation Definitions   Donating Investigator Siegfried Janz,   University of Iowa

Description
These mutant mice carry a His₆-tagged mouse Myc gene (cDNA) sequence inserted in the endogenous immunoglobulin heavy-chain 2 C-alpha locus (Igh-2). This insertion mimics the human Burkitt lymphoma t(8;14)(q24;q32) translocation and its counterpart in mice, the plasmacytoma-typical T(12;15) translocation. The His₆-tagged Myc is overexpressed in B-cells throughout B-cell development. Mutant mice develop increased numbers of B220^hiCD138⁺ plasmablasts in the bone marrow and display increased B-cell apoptosis and proliferation. 9.3% of mutant mice develop B-cell lymphomas with a mean onset of 11 months. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain may be useful in studies of 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 the cDNA sequence (lacking introns) and the first non-coding exon (with the P1/P2 promoter) of the mouse Myc gene, 1.5kb of Myc 5' flanking sequence with multiple transcription factor binding sites, the 3' UTR, an in-frame His₆, and a floxed neo selection cassette was inserted into intron 1 of the mouse Igh-2 C alpha 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 seven generations.

Control Information

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

Related Strains

Strains carrying other alleles of Myc

007693	B6(Cg)-Myctm37Mnz/J
007692	B6(Cg)-Myctm39Mnz/J
002728	B6.Cg-Tg(IghMyc)22Bri/J
021935	B6;129-Myctm1Slek/J
011001	B6;129S4-Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch/J
008332	C.129S1-Ightm1(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     (13 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Burkitt Lymphoma; BL   (MYC)

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.

Igha^tm1(Myc)Janz/Igha⁺

        involves: 129S1/Sv * C57BL/6

• tumorigenesis
• B cell derived lymphoma
  • transgenic mice display an increased incidence (9.3%) of B cell derived lymphomas with a mean onset of 330 days   (MGI Ref ID J:90901)
• hematopoietic system phenotype
• increased B cell proliferation
  • B cells proliferate about 2.5 - 3 times faster compared to normal mice   (MGI Ref ID J:90901)
• increased plasma cell number
  • B220^hiCD138⁺, putative plasmablasts, numbers are increased in the bone marrow of transgenic mice   (MGI Ref ID J:90901)
• immune system phenotype
• increased B cell apoptosis
  • B cell apoptosis is increased about 4.5 fold compared to normal B cells   (MGI Ref ID J:90901)
• increased B cell proliferation
  • B cells proliferate about 2.5 - 3 times faster compared to normal mice   (MGI Ref ID J:90901)
• increased plasma cell number
  • B220^hiCD138⁺, putative plasmablasts, numbers are increased in the bone marrow of transgenic mice   (MGI Ref ID J:90901)
• cellular phenotype
• increased B cell apoptosis
  • B cell apoptosis is increased about 4.5 fold compared to normal B cells   (MGI Ref ID J:90901)
• increased B cell proliferation
  • B cells proliferate about 2.5 - 3 times faster compared to normal mice   (MGI Ref ID J:90901)

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		Ighatm1(Myc)Janz
Allele Name		targeted mutation 1, Siegfried Janz
Allele Type		Targeted (knock-in)
Common Name(s)		iMycCalpha;
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		CJ7
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Expressed Gene		Myc, myelocytomatosis oncogene, mouse, laboratory
Gene Symbol and Name		Igha, immunoglobulin heavy constant alpha
Chromosome		12
Gene Common Name(s)		IgA; Igh-2; immunoglobulin heavy chain 2 (serum IgA);
Molecular Note		A construct consisting of a 1.5 kb of segment of genomic 5' flanking sequence from the mouse Myc gene, the first noncoding exon with the P1/P2 promoters, a mouse Myc intron-less cDNA clone with an in-frame artificial histidine tag on the 3' end, a short segment of the 3' UTR including the major polyadenylationsite, and a loxP flanked neo cassettte was inserted in opposite transcriptional orientation into intron 1 of the C alpha locus via homologous recombination. The neo cassette was subsequently removed by mating to cre transgenic mice. [MGI Ref ID J:90901]

Genotyping

Genotyping Information

Genotyping Protocols

Igh-2 ^Tm1(Myc)Janz, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Cheung WC; Kim JS; Linden M; Peng L; Van Ness B; Polakiewicz RD; Janz S. 2004. Novel targeted deregulation of c-Myc cooperates with Bcl-X(L) to cause plasma cell neoplasms in mice. J Clin Invest 113(12):1763-73. [PubMed: 15199411]  [MGI Ref ID J:90901]

Additional References

Igha^tm1(Myc)Janz related

Khuda SE; Loo WM; Janz S; Van Ness B; Erickson LD. 2008. Deregulation of c-Myc Confers distinct survival requirements for memory B cells, plasma cells, and their progenitors. J Immunol 181(11):7537-49. [PubMed: 19017943]  [MGI Ref ID J:142204]

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]

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]

Zhang W; Kater AP; Widhopf GF 2nd; Chuang HY; Enzler T; James DF; Poustovoitov M; Tseng PH; Janz S; Hoh C; Herschman H; Karin M; Kipps TJ. 2010. B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 107(44):18956-60. [PubMed: 20956327]  [MGI Ref ID J:166158]

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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

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

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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