NOD.Cg-Tg(Ins2-Cxcl13)1Cys/JbsJ

Stock number: 006154
Product name: NOD.RIP-BCL
Strain synonyms: NOD.RIP-BLC1, NOD.BLC1, NOD.BLC, NOD.RIP-BLC, RIP-BLC1
Research areas: Developmental Biology Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

Expression of the transgene in these mice leads to development of lymph node–like structures in pancreatic islets that contain B and T cell zones, high endothelial venules, stromal cells, and the chemokine SLC.

Detailed description

Ins2-Cxcl13 (commonly referred to as BLC) transgenic mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. On the B6.D2 background pancreatic islet structure is disrupted, strongly resembling severe insulitis. However, these mice have normal blood glucose levels, no decrease in B-cells and do not become overtly diabetic. Immunohistochemistry indicates Cxcl13 expression is significantly higher in the pancreatic islets than the follicular stromal cells of the lymph nodes while no expression was observed in the liver or kidney. Histopathology indicates 50% of the pancreatic islets are infiltrated with small nucleated cells. Immunohistochemistry and FACS analysis reveals that 90% of the infiltrating cells are B220+ naive B lymphcytes. In addition, CD4⁺ and CD8⁺ cells were present. Transgenic expression leads to the development of lymph node like structures that contain B and T cell zones, high endothelial venules, stromal cells and the chemokine Ccl21 (SLC), Luther SA et al; Immunity 2000.

On the NOD congenic background Tg(Ins2-Cxcl13) expression in the pancreas leads to accelerated diabetes (Donating investigator unpublished communication).

This strain is useful to the study of B cells and chemokines in the development of diabetes.

Development

Chemokine Cxcl13 (BLC) is produced by the stromal cells in lymphoid follicles. Lymphoid chemokines have a major role in homeostatic trafficking within lymphoid tissues. This transgenic strain contains the Cxcl13 cDNA fused to rat insulin promoter 7 (Ins2) injected into B6D2F1 fertilized embryos. Approximately, 19 copies of the Ins2-Cxcl13 transgene integrated into the genome. Transgenic mice resulting from B6D2F1 fertilized embyos were mated to C57BL/6 for 10 generations prior to mating to NOD for 15 genrations. In 2006, the T1DR recieved NOD.Cg-Tg(Ins2-Cxcl13)1Cys/JbsJ at generation N15 and crossed it once to NOD/LtJ (Stock# 1976).

Allele

Symbol: Tg(Ins2-Cxcl13)1Cys
Name: transgene insertion 1, Jason G Cyster
MGI accession ID: MGI:3641325
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Ins2-Cxcl13)1Cys
Marker name: transgene insertion 1, Jason G Cyster
Chromosome: UN
Strain of origin: (C57BL/6 x DBA/2)F1
Expressed genes: Cxcl13,chemokine (C-X-C motif) ligand 13,mouse, laboratory
Molecular note: The transgene comprises the full-length Cxcl13 (BLC) cDNA under control of the rat insulin 2 promoter. Immunostaining of adjacent pancreatic sections with antibodies to insulin and to CXCL13 demonstrated that all the beta cells express CXCL3; the intensity of staining for CXCL3 is several fold greater in pancreatic beta cells than in follicular stromal cells, where it is expressed from the endogenous gene. No expression is detected in liver or kidney.
General note: Three lines, having 4, 9 and 19 estimated copies of the transgene, were generated. Mice of all three lines exhibited similar B cell-enriched lymphocyte infiltration of the pancreatic beta cells. The line with 19 transgene copies, designated line 1, was used for further analyses.