B6.Cg-Tg(Emu-TXLNA)1Amjr/J

Stock number: 010914
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Research Tools

Description

Mice harboring the pEμSR-IL-14α transgene express hemagglutinin-tagged human IL-14α (TXLNA or taxilin alpha) predominantly in the B lymphocyte compartment under the direction of Eμ immunoglobulin heavy chain enhancer/SV40 promoter regions. These pEμSR-IL-14α transgenic mice may be useful in studying both autoimmune and B cell lymphoma diseases such as systemic lupus erythematosus (SLE) and Sjogren's syndrome.

Detailed description

Mice harboring the pEμSR-IL-14α transgene are viable and fertile, with expression of hemagglutinin-tagged human IL-14α (TXLNA or taxilin alpha) directed predominantly to the B lymphocyte compartment by the Eμ immunoglobulin heavy chain enhancer/SV40 promoter regions (from the pEμSR vector). Human IL-14α expression levels from the transgene are similar to mouse IL-14α expression levels observed in activated T cells/B cells. Transgene expression results in a phenotype with characteristics of systemic lupus erythematosus (SLE) and Sjogren's syndrome. Specifically, transgenic mice exhibit hypergammaglobulinemia (enhanced responses to T-dependent and T-independent antigens), autoantibodies, sialadenitis (infiltration of the parotid glands with lymphocytes), and mild immune-complex mediated nephritis with glomerular IgM deposition. In addition, almost all aged IL-14α-transgenic mice develop large B cell lymphoma (CD5+ B cell lymphoma) similar to the tumors seen in elderly patients with SLE and Sjogren's syndrome.

Development

The pEμSR-IL-14α transgene was designed with the Eμ immunoglobulin heavy chain enhancer/SV40 promoter regions (from the pEμSR vector) upstream of a hemagglutinin-tagged human IL-14α (TXLNA or taxilin alpha) cDNA sequence (human IL-14α is a cytokine encoded by the plus strand of the IL-14 gene using exons 3-10). This transgene was injected into C3H oocytes fertilized with C57BL/6J sperm. Founder mice were bred to C57BL/6J mice to establish the colony. The donating investigator reported that these pEuSR-IL-14α transgenic mice (found to harbor the transgene predominantly on chromosome 18) were backcrossed to C57BL/6J mice for more than eight generations (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Tg(Emu-TXLNA)1Amjr
Name: transgene insertion 1, Julian Ambrus Jr
MGI accession ID: MGI:4430747
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Emu-TXLNA)1Amjr
Marker name: transgene insertion 1, Julian Ambrus Jr
Chromosome: 18
Strain of origin: (C3H x C57BL/6J)F1
Expressed genes: TXLNA,taxilin alpha,human
Molecular note: The pEmuSR-IL-14alpha transgene was designed with the Emu immunoglobulin heavy chain enhancer/SV40 promoter regions (from the pEmuSR vector) upstream of a hemagglutinin-tagged human IL-14alpha (TXLNA or taxilin alpha) cDNA sequence (human IL-14alpha is a cytokine encoded by the plus strand of the IL-14 gene using exons 3-10). FISH analysis showed positive immunofluorescence on chromosome 18.