Analysis of gene expression for microminipig liver transcriptomes using parallel long-read technology and short-read...

Area of Science:

• Pharmacogenomics
• Animal Models
• Biotechnology

Background:

• Micropigs share anatomical and physiological similarities with humans, making them potential experimental models.
• Limited data exists on gene expression profiles, particularly for drug-metabolizing enzymes, in micropigs.
• Understanding these profiles is crucial for utilizing micropigs in preclinical drug development.

Purpose of the Study:

• To identify transcripts in micropig livers.
• To determine the gene expression profiles of drug-metabolizing enzymes in micropigs.
• To compare these profiles with human data and assess gender-specific differences.

Main Methods:

• Liver samples from six micropigs (three male, three female) were analyzed using parallel long-read and short-read sequencing.
• De novo assembly and expression analyses were performed on the obtained transcripts.
• Gene expression levels of phase I and phase II drug-metabolizing enzymes were quantified.

Main Results:

• A total of 50,843 transcripts were identified, with a mean contig length of 707 bp.
• Expression profiles of cytochrome P450 (P450) 1A2, 2C, 2E1, and 3A genes were similar to those in humans.
• Several phase II enzyme genes, including UDP-glucuronosyltransferase (UGT) and glutathione S-transferase (GST) variants, showed strong expression and some gender-specific differences.

Conclusions:

• Micropig liver gene expression profiles, especially for drug-metabolizing enzymes, provide a foundation for their use in drug development.
• The observed similarities to human gene expression support the micropig as a relevant preclinical model.
• Further research can leverage these findings for mechanistic studies and enhanced drug efficacy and safety evaluations.