The ALDH9A1 Knouckout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the ALDH9A1 gene has been disrupted. This loss-of-function model is generated by CRISPR/Cas9-mediated gene disruption, yielding a genetically heterogeneous pool suitable for pooled functional studies.
HAP1 is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia line, exhibiting adherent, fibroblast-like morphology. Its near-haploid karyotype simplifies gene editing and genotype-phenotype linkage, making it a preferred platform for genetic screens and functional genomics.
ALDH9A1 encodes an NAD+-dependent aldehyde dehydrogenase that catalyzes the oxidation of gamma-aminobutyraldehyde to the primary inhibitory neurotransmitter GABA, and converts 4-trimethylaminobutyraldehyde to gamma-butyrobetaine, an essential carnitine precursor. These reactions place ALDH9A1 at a critical node connecting GABA synthesis and carnitine biosynthesis. The enzyme is regulated by NFE2L2, reactive aldehydes, and PPAR??; it relies on cofactor NAD+ and processes substrates including malondialdehyde, yielding GABA, gamma-butyrobetaine, carnitine, and reduced aldehyde products. Within its signaling network, ALDH9A1 functions alongside GAD1 in GABAergic signaling and interacts with TMLHE, BBOX1, and SLC22A5 in carnitine metabolism. Consequently, gene disruption impairs GABA production, carnitine biosynthesis, and aldehyde detoxification, affecting neurotransmission and fatty acid transport.
Utilizing the HAP1 near-haploid background, this polyclonal knockout population offers clear loss-of-function phenotypes for studying aldehyde-induced cytotoxicity, GABAergic deficits, and metabolic dysregulation. The model is particularly suited for investigations into epilepsy, autism spectrum disorder, carnitine deficiency, and oxidative stress disorders, where ALDH9A1 plays a role in maintaining neurotransmitter and metabolic homeostasis.
The product supports diverse research applications, including functional genomics screens, neurobiology, and metabolic studies. Validated assays such as western blotting, RT-qPCR, GABA quantification (ELISA/HPLC), carnitine assays, and cell viability tests under aldehyde challenge (e.g., malondialdehyde exposure) can be used to characterize the knockout. High-throughput drug screening and RNA-seq are also compatible, and the polyclonal format facilitates robust, reproducible population-level analyses. For further information, please contact Ascent Research.
