The BMPR1A Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population for targeted disruption of BMPR1A in the human near-haploid HAP1 cell line. This product provides a heterogeneous pool of cells with loss-of-function mutations, enabling robust gene disruption studies without clonal isolation and minimizing clonal bias. The polyclonal format facilitates experiments requiring population-level responses, making it a versatile model for investigating BMPR1A-dependent signaling.
HAP1 is a near-haploid human cell line derived from the male KBM-7 chronic myeloid leukemia line, belonging to the myeloid hematopoietic lineage. Its haploid karyotype simplifies genetic manipulation, allowing single-allele targeting to achieve functional gene knockout and eliminating the complexity of biallelic editing. This background is well-suited for knockout studies in cell biology, cancer research, and signal transduction, providing a relevant myeloid context for hematopoietic signaling analysis.
BMPR1A encodes a type I BMP receptor serine/threonine kinase that responds to ligands such as BMP2, BMP4, BMP7, and GDF5. Ligand engagement induces complex formation with BMPR2, leading to phosphorylation of SMAD1/5/8, which then partners with SMAD4 to translocate to the nucleus and transcriptionally activate targets like ID1, ID2, ID3, and RUNX2. Signaling is modulated by inhibitors including Noggin, Chordin, and SMAD6/7, and intersects with TGF-beta and MAPK pathways. Receptor activity is fine-tuned by interacting proteins FKBP12, JAK2, and XIAP, while SMURF1/2 mediate ubiquitin-dependent turnover.
In the myeloid leukemia HAP1 background, BMPR1A knockout illuminates BMP-regulated hematopoietic processes such as differentiation, proliferation, and apoptosis. Given its roles in juvenile polyposis syndrome, colorectal cancer, and bone disorders, this model enables dissection of tumor-suppressive or oncogenic BMP signaling in hematologic malignancies. The haploid genome amplifies phenotypic consequences of gene disruption, facilitating clear analysis of SMAD-dependent transcription and cross-talk with JAK-STAT or MAPK pathways.
Research applications include BMP signaling dissection, high-throughput drug screening for SMAD transcriptional modulators, and mechanistic cancer and bone biology studies. Key assays with this model include western blotting for phospho-SMAD1/5/8, RT-qPCR of ID1/2, BRE-luciferase reporter assays, SMAD4 nuclear translocation immunofluorescence, RNA-seq, flow cytometry, alkaline phosphatase assays, and migration assays. This product supports fundamental and applied research, including drug discovery. For further information, contact Ascent Research.
