C57BL/6-Tg(SV40-Sox11,-EGFP)2Spare/J

Stock number: 037185
Product name: Eμ-SOX11 Tg
Research areas: Cancer Research, Research Tools

Description

Eμ-SOX11 transgenic mice express the mouse Sox11 (SRY-box transcription factor 11) sequence and an EGFP reporter in B cells. SOX11 overexpression in B cells results in B-cell hyperplasia and a CD5+CD19+CD23- immunophenotype found in mantle cell lymphoma (MCL) patients. This strain may be useful for studying B-cell receptor signaling, MCL disease biology and preclinical drug development.

Detailed description

Sox11 (SRY (sex determining region Y)-box 11) encodes a high-mobility transcription factor involved in brain and nerve cell development as well as B cell development. SOX11 is overexpressed in the majority of mantle cell lymphoma (MCL) patients (78%-93%) and is considered an MCL-specific oncogene. MCL is an aggressive, often fatal, B-cell lymphoma characterized by increased B cell receptor signaling and sensitivity to BTK (Bruton tyrosine kinase) inhibition.

Eμ-SOX11 transgenic mice express the mouse Sox11 sequence and an EGFP reporter (as a marker of transgene expression) under the control of the B cell specific (Igh) Eμ enhancer and an SV40 promoter. Mice hemizygous for the transgene are viable and fertile. Hemizygotes develop enlarged spleens and oligoclonal B-cell hyperplasia in spleen, bone marrow and peripheral blood as early as 1.5 months of age. The increase in B cells is restricted to CD5+CD19+CD23- cells (B1a B cells). BCR signaling is increased in Eμ-SOX11 transgenic mice at baseline levels and is further increased by anti-IgM stimulation. The donating investigator indicates that EGFP cannot be visualized by direct fluorescence. This strain may be useful for studying B-cell receptor signaling, MCL disease biology and preclinical drug development.

Development

The Eμ-SOX11 transgenic construct contains a B-cell specific (Igh) Eμ enhancer and an SV40 promoter directing expression of mouse Sox11 full length sequence, an IRES2 and an EGFP reporter followed by a polyA sequence. The linearized construct was microinjected into the pronuclei of fertilized C57BL/6 oocytes. Founder line 2 was established and backcrossed to C57BL/6J by the donating laboratory (see SNP note below). Insertion site and copy number is unknown. Upon arrival in February 2024, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

In 2024, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 males sent to The Jackson Laboratory Repository. All five of the 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 mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Tg(SV40-Sox11,-EGFP)2Spare
Name: transgene insertion 2, Samir Parekh
MGI accession ID: MGI:7567455
Generation method: Transgenic
Attributes: Reporter; Inserted expressed sequence
Synonyms: Emu-SOX11 Tg
Marker symbol: Tg(SV40-Sox11,-EGFP)2Spare
Marker name: transgene insertion 2, Samir Parekh
Chromosome: UN
Strain of origin: C57BL/6
Molecular note: The transgenic construct contains a B-cell specific (Igh) Emu; enhancer and an SV40 promoter directing expression of mouse Sox11 full length sequence, an IRES and an EGFP reporter followed by a polyA sequence.