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Expression of FAM159B in Humans, Rats, and Mice: A Cross-species Examination
Anna-Sophia Liselott Beyer1, Daniel Kaemmerer2, Jörg Sänger3
1Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany.
Abstract:
Little is known about the adaptor protein FAM159B. To determine whether FAM159B expression findings in rats or mice can be extrapolated to humans, we compared FAM159B expression in healthy tissue samples from all three species using immunohistochemistry. Despite variations in expression intensity, similar FAM159B expression patterns were observed in most organs across species. The most prominent species difference was noted in pancreatic islets; while FAM159B expression was limited to single cells on the outer edges in mice and rats, it was detectable across entire islets in humans. Double-labeling immunohistochemistry revealed partial overlap of FAM159B expression with that of insulin, glucagon, and somatostatin in human islets. By contrast, FAM159B showed complete colocalization with only somatostatin in rats and mice. An additional analysis of FAM159B expression in lean and obese Zucker rats revealed larger islet areas due to increased β-cell mass in obese rats, which was accompanied by a smaller percentage of FAM159B-positive δ-cells per islet area. Beyond the known differences in islet architecture across species, our results point to larger dissimilarities in blood glucose regulation between rodents and humans than generally assumed. Moreover, findings regarding FAM159B expression (and function) cannot be directly transferred between rodents and humans.
Insights
Researchers compared adaptor protein FAM159B expression across species. Human pancreatic islet cells show distinct FAM159B patterns compared to rodents, indicating differences in blood glucose regulation and limiting direct translation of rodent findings.
Area of Science:
- Endocrinology and Metabolism
- Cell Biology
- Comparative Physiology
Background:
- The adaptor protein FAM159B function and expression patterns are largely uncharacterized.
- Understanding species-specific protein expression is crucial for accurate preclinical research translation.
Purpose of the Study:
- To compare FAM159B expression in human, rat, and mouse tissues.
- To investigate potential species-specific differences in FAM159B localization, particularly within pancreatic islets.
- To assess the translatability of rodent FAM159B findings to human physiology.
Main Methods:
- Immunohistochemistry was employed to detect FAM159B protein expression in healthy tissue samples from humans, rats, and mice.
- Double-labeling immunohistochemistry was used to examine the colocalization of FAM159B with islet hormones (insulin, glucagon, somatostatin).
- FAM159B expression was analyzed in lean and obese Zucker rats to investigate its relationship with islet architecture and cell mass.
Main Results:
- Similar FAM159B expression patterns were observed in most organs across species, despite variations in intensity.
- A significant species difference was identified in pancreatic islets: FAM159B localized to outer-edge cells in rodents but spanned entire islets in humans.
- In human islets, FAM159B partially overlapped with insulin, glucagon, and somatostatin. In rodents, it colocalized only with somatostatin.
- Obese rats showed increased islet area and beta-cell mass, with a reduced percentage of FAM159B-positive delta-cells per islet area.
Conclusions:
- FAM159B expression in pancreatic islets differs substantially between humans and rodents.
- These species-specific differences suggest greater dissimilarities in blood glucose regulation than commonly assumed.
- Research findings on FAM159B expression and function cannot be directly extrapolated from rodents to humans.
