B6.Cg-Tg(Igh-R4AVh/Ighm^a)1Dmnd/SptzMmjax

Stock number: 025063
Product name: R4A-Cμ
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

Mice hemizygous for the R4A-Cu transgene express the IgM heavy chain of the R4A anti-dsDNA antibody. Transgenic heavy chain expressing B cells (IgM^a) maintain tolerance in the periphery by deletion and anergy and exhibit arrested development and a shortened lifespan. These mice may be useful in for studying the regulation of autoreactive (IgM anti-dsDNA) B cells.

Detailed description

Mice hemizygous for the R4A-Cu transgene are viable and fertile and express the IgM heavy chain of the R4A anti-dsDNA antibody. Transgenic heavy chain expressing B cells (IgM^a) represent the majority of B cells in the bone marrow and spleen. Absolute numbers of B cells in the bone marrow and spleen are reduced as compared to non-transgenic controls. These B cells maintain tolerance in the periphery by deletion and anergy. They exhibit characteristics of anergic B cells including arrested development, shortened lifespan and reduced surface expression of the B cell receptor. Transgenic B cells cannot be induced to secrete antibody by crosslinking, however, activation can be achieved in vitro by T-cell derived factors.

These mice may be useful in for studying the regulation of autoreactive (IgM anti-dsDNA) B cells.

Development

This transgene contains the unmutated, rearranged immunoglobulin V-D-J and heavy chain enhancer region from the anti-dsDNA producing hybridoma R4A, comprising the S107 V11 heavy chain gene and a Vk1 light chain gene, ligated to a 9.9 kb fragment from all (membrane and secreted) the exons of the Igh-mu constant region (Cu) from BALB/c, which is of the Ighm^a allotype. The transgenic vector was introduced to (C57BL/6 x CBA)F1 embryos. Founders were backcrossed to the NZW inbred strain for 10 generations. Mice from the colony were transferred to Dr. Linda Spatz at The City College of New York and then backcrossed to C57BL/6 for more than 20 generations (see SNP note below). This line carries 5 copies of the transgene.

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 mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Tg(Igh-R4AVh/Ighm^a)1Dmnd
Name: transgene insertion 1, Betty Diamond
MGI accession ID: MGI:5569385
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Igh-R4AVh/Ighm^a)1Dmnd
Marker name: transgene insertion 1, Betty Diamond
Chromosome: UN
Strain of origin: (C57BL/6 x CBA)F1
Expressed genes: Ighm,immunoglobulin heavy constant mu,mouse, laboratory
Molecular note: This transgene contains the unmutated, rearranged immunoglobulin V-D-J and heavy chain enhancer region from the anti-dsDNA producing hybridoma R4A, comprising the S107 V11 heavy chain gene and a Vk1 light chain gene, ligated to a 9.9 kb fragment from all (membrane and secreted) the exons of the Igh-mu constant region (Cu) from BALB/c, which is of the Ighm^a allotype. Southern blot analysis indicates that the transgene integrated in a single site of the genome. There are 5 copies of the transgene.