The HPS6 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the HPS6 gene has been disrupted to generate a loss-of-function model. This product comprises a heterogeneous pool of HAP1 cells carrying a range of HPS6 gene edits, providing a robust tool for studying the functional consequences of HPS6 deficiency without the need for single-cell clone isolation. The polyclonal format preserves the diversity of the edited population, enabling experiments that benefit from a broad representation of knockout variants while maintaining the genetic simplicity of the host cell line.
HAP1 is a near-haploid human cell line derived from the male chronic myeloid leukemia line KBM-7. Its near-haploid karyotype makes it exceptionally well-suited for genetic screens and knockout studies, as the presence of a single copy of most genes allows for straightforward interpretation of genotype?Cphenotype relationships. HAP1 cells retain core signaling and trafficking pathways of leukemic cells, providing a biologically relevant context for studying gene function in lysosome-related organelle biology while offering the experimental advantages of haploidy.
HPS6 encodes a subunit of the biogenesis of lysosome-related organelles complex-2 (BLOC-2), a multi-protein complex essential for the formation of specialized organelles such as melanosomes and platelet dense granules. HPS6 is transcriptionally regulated by MITF and TFEB, master regulators of lysosomal and melanosomal gene expression, and it physically interacts with HPS3 and HPS5 to assemble the functional BLOC-2 complex. Downstream of this complex, cargoes including TYR, TYRP1, and serotonin are properly trafficked to maturing organelles; disruption of HPS6 consequently leads to impaired melanin synthesis and defective platelet granule biogenesis, recapitulating molecular hallmarks of Hermansky-Pudlak syndrome type 6.
The near-haploid nature of HAP1 cells eliminates the confounding effects of a second wild-type allele, ensuring that disruption of HPS6 yields a clean loss-of-function phenotype. This knockout model is particularly valuable for dissecting the assembly and function of the BLOC-2 complex, trafficking routes mediated by AP-3 and LAMP1, and the transcriptional networks governed by MITF and TFEB. It provides a genetically defined background to study the cell biology of oculocutaneous albinism and platelet dense granule deficiencies, linking molecular defects to disease-relevant phenotypes.
Key research applications include modeling Hermansky-Pudlak syndrome type 6, investigating melanosome trafficking and maturation, and studying platelet dense granule formation in a haploid genetic background. Representative assays that can be performed with these cells include western blotting for HPS6, HPS3, and HPS5; immunofluorescence microscopy for LAMP1 and TYR to assess lysosome-related organelle distribution; RT-qPCR to quantify MITF/TFEB target gene expression; and functional assays such as melanosome distribution analysis and platelet aggregation studies. Additional uses encompass drug sensitivity screens and genome-wide haploid genetic screens to identify modifiers of the HPS6 phenotype. For further details and ordering information, please contact Ascent Research.
