IL1A is a pleiotropic cytokine involved in various immune responses, inflammatory macrophage pro-inflammatory processes, and hematopoiesis. IL1A is produced by monocytes and macrophages as a proprotein, which is proteolytically processed and released in response to cell injury, thereby inducing apoptosis.
The exons 2-7 of the mouse Il1a gene that encode the whole molecule (from ATG to the STOP codon) are replaced by human counterparts in B-hIL1A mice. The promoter, 5’ UTR, and 3’ UTR regions of the mouse gene are retained. The human IL1A expression is driven by the endogenous mouse Il1a promoter, while the transcription and translation of the mouse Il1a gene will be disrupted. Human IL1A was exclusively detectable in the monocytes of homozygous B-hIL1A mice.
Additionally, IL-1A plays an important role in rheumatoid arthritis, Alzheimer's disease and related vascular dementia, diabetes, periodontal disease, systemic sclerosis, autoimmune encephalomyelitis, and cerebral infarction.
Targeting strategy
Gene targeting strategy for B-hIL1A mice. The exons 2-7 of mouse Il1a gene that encode the whole molecule (ATG to STOP codon) are replaced by human counterparts in B-hIL1A mice. The promoter, 5’UTR and 3’UTR region of the mouse gene are retained. The human IL1A expression is driven by endogenous mouse Il1a promoter, while mouse Il1a gene transcription and translation will be disrupted.
Protein expression analysis in cellular supernatant
Strain specific IL1A expression analysis in wild-type C57BL/6JNidfc mice and homozygous humanized B-hIL1A mice by ELISA. Monocytes derived from bone marrow were collected from wild-type C57BL/6JNidfc mice (+/+) and homozygous B-hIL1A mice (H/H) (female, n=3, 10-week-old) stimulated with 1 μg/mL LPS in vivo for 24 hrs. Expression level of mouse and human IL1A were analyzed by ELISA (anti-mouse IL-1a ELISA kit: Biolegend, 433404; anti-human IL-1A ELISA kit: Biolegend, 445807). Mouse IL1a was only detectable in wild-type C57BL/6Nidfc mice. Human IL1A was exclusively detectable in homozygous B-hIL1A mice. Values are expressed as mean ± SEM.