C57BL/6-Igkc^tm1Cgn Tg(IgkV3-2*01)L16Fosm/J

Stock number: 031839
Product name: mLCV3-Tg/kKO
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These mLCV3-Tg transgenic/Igkc KO mice (mLCV3-Tg/kKO) express autoantibodies to the glomerular and alveolar basement membrane noncollagenous domain 1 (NC1) of the α 3 chain of type IV collagen as well as joint cartilage type II collagen, and develop an anti-collagen autoimmune response. The lack of endogenous Igkc expression allows transgene expression tracking. These mice may be suitable for use in studies related to autoimmune diseases such as Goodpasture’s disease and rheumatoid arthritis.

Detailed description

These mLCV3-Tg /kKO mice carry a transgene containing a rearranged V-J-C immunoglobulin kappa light chain derived from monoclonal antibodies that bind to the glomerular and alveolar basement membrane noncollagenous domain 1 (NC1) of the α 3 chain of type IV collagen and to joint cartilage type II collagen, and a knock-out allele of Igkc. Transgene expression is detected on the surface of splenic B cells and in the serum by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Unchallenged mLCV3-Tg /kKO mice spontaneously produce autoantibodies to alpha3(IV)NC1 collagen, and occasional granular Ig deposition in kidneys, but no clinical signs or symptoms of disease. Toll-like receptor ligands induce isolated splenocytes from mLCV3-Tg /kKO mice to produce autoantibodies to alpha3(IV)NC1 and citrullinated type II collagens. The lack of endogenous Igkc expression allows transgene expression tracking. Mice that are hemizygous for the transgene and homozygous for the Igkc^tm1Cgn allele are viable and fertile. Homozygous viability/fertility for the transgene has not been tested (May 2018).

Development

The mLCV3-Tg transgene contains genomic DNA of the rearranged IGKV3 immunoglobulin kappa light chain (Igk) gene, encoding the mAb IGKV3-2*01(former Vk21C)/Jk2 kappa light chain. The transgenic construct was injected into fertilized C57BL/6NHsd mouse eggs. Founder line L16 was subsequently established. The mice were then backcrossed to C57BL/6J for 10 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Transgenic mice were then crossed to C57BL/6-Igkc^tm1Cgn/J (Stock No. 002400) mice generating these mLCV3-Tg/kKO mice. The mLCV3-Tg/kKO double mutant mice were maintained as hemizygous for the transgene and homozygous for the Igkc^tm1Cgn allele. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Igkc^tm1Cgn
Name: targeted mutation 1, University of Cologne
MGI accession ID: MGI:1857188
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: CkappaT; kappa-
Marker symbol: Igkc
Marker name: immunoglobulin kappa constant
Marker synonyms: D4Mit8; HCAK1; Igk@; IGKCD; Km
Chromosome: 6
Strain of origin: C57BL/6
Molecular note: A neomycin resistance cassette replaced the exon encoding the constant region of the immunoglobulin kappa chain, its splicing signal and polyadenylation site.

Allele

Symbol: Tg(IgkV3-2*01)L16Fosm
Name: transgene insertion L16, Mary Foster
MGI accession ID: MGI:6156582
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: IGKV3 LC Tg; mLCV3-Tg
Marker symbol: Tg(IgkV3-2*01)L16Fosm
Marker name: transgene insertion L16, Mary Foster
Chromosome: UN
Strain of origin: C57BL/6NHsd
Expressed genes: Igkv3-2,immunoglobulin kappa variable 3-2,mouse, laboratory
Site of expression: Transgene expression is detected on the surface of splenic B cells and in the serum.
Molecular note: The transgene comprises the rearranged IGKV3-2*01 (formerly Vk21C)/Jk2 immunoglobulin kappa light chain from a hybridoma cell line. It encodes the light chain of antibodies generated in C57BL/6 mice against the antigenic NC1 domain from collagen type IV, alpha 3 (anti-alpha3(IV)NC1).