The GRN Knouckout HAP1 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout population generated from the HAP1 cell line through targeted disruption of the GRN gene. As a polyclonal pool, it encompasses a heterogeneous mixture of knockout genotypes, providing a robust loss-of-function model that avoids the biases of single-cell cloning and enables the study of GRN-dependent biology in a physiologically relevant, bulk cell population.
HAP1 is a human near-haploid cell line derived from the chronic myeloid leukemia line KBM-7, characterized by a stable haploid karyotype that simplifies genetic manipulation and facilitates unambiguous interpretation of knockout phenotypes. Due to its haploid genome, HAP1 is a widely adopted platform for functional genomics, large-scale CRISPR screens, and drug target validation, offering rapid growth and compatibility with high-throughput screening formats.
Progranulin (GRN) is a secreted glycoprotein that signals through TNFR2 and EphA2 receptors to activate PI3K/Akt and MAPK/ERK pathways, phosphorylating Akt and ERK and modulating GSK3?? and mTOR to promote survival and proliferation. It is internalized by sortilin (SORT1)-mediated endocytosis and delivered to lysosomes, where it interacts with PSAP to regulate hydrolases like CTSD and maintain LAMP1-dependent structural integrity, thereby controlling lysosomal function and autophagy. Progranulin expression is regulated by TFEB and induced by TNF-??, IL-1??, and ER stress, linking inflammatory signals to lysosomal homeostasis.
Disruption of GRN in the HAP1 background creates a tractable cellular model to investigate the dual roles of progranulin in signaling and lysosome biology. This system is directly relevant to neurodegenerative diseases: loss-of-function GRN mutations cause frontotemporal dementia, and deficient progranulin leads to lysosomal dysfunction characteristic of neuronal ceroid lipofuscinosis. In cancer, progranulin??s survival signaling through Akt and ERK pathways is often upregulated, making the knockout model valuable for studying tumor cell maintenance. The near-haploid nature of HAP1 ensures clean phenotypic readouts and isogenic comparisons.
The polyclonal knockout pool is suitable for diverse applications including functional genomics screens to identify genetic interactors of GRN, detailed phospho-signaling analysis of the PI3K/Akt and MAPK/ERK pathways, and immunofluorescence-based examination of lysosomal markers such as LAMP1 and CTSD. It can be employed in drug screening campaigns targeting progranulin-mediated survival or in reporter assays to monitor pathway activity. Standard biochemical assays??western blotting, RT-qPCR, flow cytometry, and apoptosis assays??are fully compatible. For further information and technical support, please contact Ascent Research.
