TWEAK is a 27kDa protein also known as tumor necrosis factor superfamily member 12 (TNFSF12), TNF-related weak inducer of apoptosis, and CD255. TWEAK is a type II transmembrane protein with strong homology to TNF in its extracellular portion, though less potent in inducing apoptosis. TWEAK transcript is expressed broadly in many adult and fetal tissues, however, the staining of human peripheral blood mononuclear cells with TWEAK-specific antibodies shows a more restricted pattern. TWEAK is expressed as membrane-bound and secreted forms, the soluble form is produced by proteolytic processing. TWEAK binds to the TWEAK receptor, FN14, to induce apoptosis, NF-κB translocation, and promote angiogenesis and endothelial cell proliferation. It has also been implicated in the induction of inflammatory cytokines.
APRIL is a member of the TNF ligand superfamily. It is synthesized as a 32kDa type II transmembrane protein which is cleaved by furin in the Golgi to release a 17 kDa soluble molecule. Secreted APRIL consists almost entirely of a single TNF homology domain. Little or no transmembrane APRIL is expressed on the cell surface. Both APRIL and the closely related protein BAFF signal through the TNF superfamily receptors TNFRSF13b/TACI and TNFRSF17/BCMA to promote cellular proliferation and protect from apoptosis. A bioactive cell surface-expressed protein known as TWEPRIL consists of the intracellular domain, transmembrane segment, and stalk region of TWEAK fused to the TNF homology domain of APRIL.
The full sequence of mouse Tweak gene and mouse April gene were replaced with the corresponding human sequences in B-hTWEAK/hAPRIL mice.
Protein expression analysis
Strain specific TWEAK expression analysis in homozygous B-hTWEAK/hAPRIL mice by western blot.
Lung was collected from wild-type C57BL/6 mice (+/+) and homozygous B-hTWEAK/hAPRIL mice (H/H), and analyzed by western blot with anti-TWEAK antibody, which has cross reaction between human TWEAK and mouseTWEAK. TWEAK was detectable both in wild-type mice and homozygous B-hTWEAK/hAPRIL mice.
Strain specific APRIL expression analysis in heterozygous B-hTWEAK/hAPRIL mice by flow cytometry.
Splenocytes were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hTWEAK/hAPRIL mice (H/H), and analyzed by flow cytometry with anti-APRIL antibody, which has cross reaction between human APRIL and mouse APRIL. APRIL was detectable both in wild-type mice and homozygous B-hTWEAK/hAPRIL mice.