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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. 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. 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. 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.

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