Immunology

Mutation in the rat interleukin 34 gene impacts macrophage development, homeostasis, and inflammation

Ethan Littlefield

05 Jul 2025 — 1 min read

PMCID: PMC12177736

PMID: 40533345

DOI: 10.26508/lsa.202503264

Journal: Life science alliance

Publication Date: 2025-6-18

Authors: Huang S, Patkar OL, Schulze S, Carter-Cusack D, Millard S, et al.

Key Points

IL34 deficiency leads to selective microglial depletion in grey matter brain regions
Heterozygous Il34+/- rats demonstrate partial loss of grey matter microglia
Microglia appear non-essential for normal postnatal neurodevelopment in rats

Summary

This comprehensive study investigated the functional roles of IL34 in rat physiology, focusing on its interaction with CSF1R and impact on tissue-resident macrophage populations. By generating Il34-/- rats using CRISPR-Cas9 technology, researchers systematically characterized the molecular and cellular consequences of IL34 loss across multiple organ systems, with particular emphasis on microglial populations in the brain.

The most significant finding was a subtle but selective depletion of microglia in grey matter regions, demonstrating that IL34 plays a nuanced role in maintaining microglial homeostasis. Unlike previous mouse models, the rat study revealed a more complex relationship between IL34 and CSF1, suggesting potential compensatory mechanisms and tissue-specific variations in macrophage maintenance. Critically, the researchers found no significant developmental or behavioral abnormalities in Il34-/- rats, indicating that microglia may not be essential for normal postnatal neurodevelopment.

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