Lacrimal Gland and Orbital Lesions in Lat^Y136F Knock-in Mice, a Model for Human IgG4-Related Ophthalmic Disease

Abstract

Purpose

Lat^Y136F knock-in mice were recently proposed as an animal model for immunoglobulin G4 (IgG4)-related disease. In this study, we investigated whether Lat^Y136F knock-in mice exhibit ophthalmic lesions, specifically in the lacrimal and Harderian glands.

Methods

Lacrimal glands, Harderian glands, and adherent lymphoid follicle lesions were dissected from Lat^Y136F knock-in mice and wild type (WT) C57BL/6 mice between 6 and 24 weeks of age. Tissues were stained with hematoxylin-eosin, immunoglobulin G (IgG), and anti-IgG1, a homologue of human IgG4, for histopathological analysis.

Results

In Lat^Y136F knock-in mice, IgG1-positive cells infiltrated the space between the lacrimal gland acinar cells at 6, 9, 12, and 20 weeks or order, and the number of IgG1-positive cells did not differ significantly between these age groups. Infiltration of IgG1-positive inflammatory cell was also observed in the Harderian glands of Lat^Y136F knock-in mice at all ages. The ratio of IgG1/IgG-positive cells averaged 80 and 67% in the lacrimal and Harderian glands, respectively. Dense IgG1-positive lesions were also seen in tissues adjacent to the lacrimal and Harderian glands in some Lat^Y136F knock-in mice. In contrast, there were almost no IgG1-positive cell infiltrates in the lacrimal and Harderian glands of WT mice.

Conclusion

IgG1-positive cells infiltrate the lacrimal and Harderian glands of Lat^Y136F knock-in mice, indicating that Lat^Y136F knock-in mice could be a representative animal model for IgG4-related ophthalmic disease.

Keywords:

• IgG4 related disease
• lacrimal gland
• mouse
• Harderian gland
• orbit

Acknowledgments

The authors thank Ryoko Yamagishi for her technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, MT, upon reasonable request.

Additional information

Funding

This work was partially supported by the Research Program of Intractable Diseases of the Ministry of Health, Labor, and Welfare of Japan, JSPS KAKENHI [Grant Number 26461487 and 17K09999].