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The twitcher mouse: immunocytochemical study of Ia expression in macrophages
Y Higashi1, A Komiyama, K Suzuki
1Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27599-7525.
Insights
Immune response associated antigen (Ia) positive cells in the twitcher mouse model of globoid cell leukodystrophy suggest a subset of macrophages within the central nervous system. Further research is needed to determine their origin.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Globoid cell leukodystrophy is a human lysosomal storage disorder.
- The twitcher mouse serves as an authentic animal model for studying this disease.
- Understanding the cellular mechanisms in the nervous system is crucial for disease progression insights.
Purpose of the Study:
- To investigate the characteristics and origin of immune response associated antigen (Ia) positive cells in the nervous system of twitcher mice.
- To differentiate between endogenous microglia and infiltrated cells in the context of globoid cell leukodystrophy pathology.
- To explore the role of Mac-1 antigen expression in these cells.
Main Methods:
- Immunocytochemistry using monoclonal antibodies against Mac-1 antigen.
- Immunoelectron microscopy to examine cellular ultrastructure.
- Morphological analysis of cells in the central and peripheral nervous systems.
Main Results:
- Numerous Mac-1 positive cells were identified in both the central and peripheral nervous systems.
- Ia positive cells were predominantly found in the white matter, with approximately 10% co-expressing Mac-1.
- Both Ia positive and Mac-1 positive cells exhibited cytoplasmic vacuoles with tubular inclusions characteristic of globoid cell leukodystrophy.
Conclusions:
- Ia positive cells in the twitcher mouse CNS appear to be a subset of macrophages.
- The findings suggest a potential role for these cells in the pathology of globoid cell leukodystrophy.
- The origin of Ia expressing cells (endogenous microglia vs. exogenous infiltration) requires further investigation.
Abstract:
The cells expressing immune response associated antigen (Ia) were investigated in the nervous system of the twitcher mouse (an authentic murine model of globoid cell leukodystrophy in humans). With immunocytochemistry using a monoclonal antibody against Mac-1 antigen, many Mac-1 immunoreactive cells (Mac-1 positive cells) were detected in the central as well as the peripheral nervous systems (CNS and PNS). In the CNS, Mac-1 positive cells in the gray matter showed cellular morphology of ramified microglia with delicate cellular processes, while in the white matter Mac-1 positive cells were more plump in shape. Ia expressing cells (Ia positive cells) were also largely confined to the white matter. About 10% of the Mac-1 positive cells were Ia positive. The Ia and Mac-1 positive cells were slender and spindle shaped, and morphologically similar to Ia positive cells in the peripheral nerves while the cells expressing Mac-1 only were more plump in shape. With immunoelectron microscopy, however, both slender Ia positive and plump Ia negative and Mac-1 positive cells revealed electron lucent cytoplasmic vacuoles containing characteristic tubular inclusions of globoid cell leukodystrophy. The results suggest that Ia positive cells are a subset of macrophages in the CNS. Whether Ia expression was induced to "endogenous" microglia or whether Ia expressing cells were exogenous cells infiltrated in the CNS in response to pathological lesions is yet to be determined.