FAH2 Antibody

Definition and Biological Context

The FAH2 antibody targets the fumarylacetoacetate hydrolase (FAH) enzyme, a critical protein in tyrosine catabolism. FAH deficiency causes hereditary tyrosinemia type I (HTI), a metabolic disorder leading to liver failure and hepatocellular carcinoma . In research, FAH2 antibodies are used to detect FAH expression in experimental models, such as CRISPR-Cas9-edited hepatocytes, to validate gene correction .

CRISPR-Cas9 Gene Editing Validation

• In a mouse model of HTI (Fah^mut/mut), FAH2 antibodies were used to confirm the restoration of FAH expression after CRISPR-Cas9-mediated correction .

  • Immunohistochemistry: Showed 33.5% ± 3.3% FAH-positive hepatocytes 30 days post-treatment .

  • Initial Repair Rate: 0.40% ± 0.12% of hepatocytes showed FAH expression when measured 6 days post-treatment .

Sphingolipid Metabolism Studies

• FAH2 (fatty acid hydroxylase 2) is also implicated in sphingolipid biosynthesis. Mutations in FAH1/2 reduce 2-hydroxy sphingolipids in plant plasma membranes, altering lipid droplet dynamics . While FAH2 antibodies are not explicitly mentioned here, their use could help elucidate FAH2’s role in lipid regulation .

HTI Treatment

• CRISPR-Cas9 delivery with FAH2-targeting guide RNAs restored FAH function in Fah^mut/mut mice, enabling survival after NTBC (tyrosine catabolism inhibitor) withdrawal .

• Efficacy Metrics:

  • RT-PCR confirmed FAH mRNA levels at 8–36% of wild-type mice post-treatment .

  • Deep sequencing revealed a 9% A→G correction rate in FAH2-treated livers .

Antibody Validation in Disease Models

• FAH2 antibodies are critical for assessing functional recovery in gene-edited tissues, as shown by reduced hepatocyte toxicity and improved survival in HTI models .

Table 1: FAH2 Antibody Applications in HTI Research

Table 2: Sphingolipid Alterations in FAH1/2 Mutants

Challenges and Future Directions

• Off-Target Effects: CRISPR-Cas9 editing with FAH2 guide RNAs showed a 26% indel rate in treated hepatocytes, necessitating improved specificity .

• Functional Assays: Further studies are needed to link FAH2 antibody signals to enzymatic activity and long-term metabolic outcomes .