B6.Cg-Tg(LCKprBCL2L1)12Sjk/J

Stock number: 013738
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These lck^pr-bcl-X_L transgenic mice express a human BCL2L1 cDNA sequence under the control of a mouse Lck promoter. These mice may be used for studying development, maturation, and apoptosis of thymocytes.

Detailed description

These lck^pr-bcl-X_L transgenic mice express a human B-cell leukemia/lymphoma 2 like, 1 (BCL2L1 or BCL-XL) cDNA sequence, under the control of a mouse lymphocyte protein tyrosine kinase proximal promoter (Lck^pr). Mice that are heterozygous for this transgene are viable, fertile, and normal in size. Lck^pr drives BCL-XL expression within all thymocyte subsets and protects thymocytes from a variety of apoptotic stimuli, including γ irradiation, glucocorticoids, and anti-CD3 treatment. This BCL-XL overexpression alters thymocyte maturation, resulting in an increase in CD3^int/hi and a decrease in CD3^lo thymocytes, along with an increase in intermediate CD4⁺8^lo and CD4^lo8⁺ thymocytes. They also exhibit an increase in single positive CD8 T cells in the spleen. Overexpression of BCL-XL causes down-regulation of B-cell leukemia/lymphoma 2 (BCL-2) and represses cell death observed in BCL-2 null mice, suggesting a redundant cell survival pathway. These mice may be used for studying development, maturation, and apoptosis of thymocytes.

Development

The LCKprBCL2L1 transgene was designed with the human B-cell leukemia/lymphoma 2 like, 1 (BCL2L1) cDNA driven by a mouse lymphocyte protein tyrosine kinase (Lck) proximal promoter, followed by a human growth hormone (hGH) gene and a simian virus 40 (SV40) polyadenylation site. The transgene was microinjected into fertilized oocytes, and mice from founder line 12 were bred to C57BL/6J mice for at least 10 generations to generate a colony of lck^pr-bcl-x_L mice. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony.

Allele

Symbol: Tg(LCKprBCL2L1)12Sjk
Name: transgene insertion 12, Stanley J Korsmeyer
MGI accession ID: MGI:2447593
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(LCKprBCL2L1)12Sjk
Marker name: transgene insertion 12, Stanley J Korsmeyer
Chromosome: UN
Strain of origin: Not Specified
Expressed genes: BCL2L1,BCL2 like 1,human
Molecular note: The transgene consists of 0.75 kb of Lck proximal promoter sequences and 0.8 kb of human BCL2L1 cDNA. Introns, exons, and polyadenylation sequences from the human growth hormone gene consitutes the 3' untranslated region of the construct. The Lck promoter was used to drive transgene expression in lymphoid tissues. Transgene expression in the thymus and spleen was verified by Western blot analysis and flow cytometry.
General note: Transgenic lines 12 and 24, which expressed high amounts of the transgene, were established. Most of the analysis was performed using line 12 and confirmed with line 24.