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S. Wasmuth, M. Hundelt, R. Brandt, D. Bauer, A. Heiligenhaus, D. Pauleikhoff; Variation in Eyes of Mice Transgenic for the Human Tau Protein. Invest. Ophthalmol. Vis. Sci. 2007;48(13):24.
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Transgenic mice that express the human tau protein under the control of the CaMKIIalpha promotor serve as a model for Alzheimer’s disease (AD). AD and age-related macular degeneration (AMD) share some common features: they generally appear in elder individuals, several kinds of deposits are of importance, there is a role for complement activation and growing evidence for underlying inflammatory processes. In this study eyes of these transgenic mice were examined for retinal histological changes, for the retinal expression of the transgenic tau protein and sub-RPE deposits as observed in AMD.
Two transgenic mice strains were generated on C57/BL6 background. While 4wt1 mice expressed the longest isoform of human wildtype tau protein, 4php3 mice expressed a pseudohyperphosphorylated form of the human tau protein. Age-matched wildtype C57/BL6 mice eyes were examined as a control. Paraffin sections of eyes from 22 month old mice were stained with hematoxylin eosin (HE) and periodic schiff’s acid (PAS) in order to investigate the histology. For confirmation of fatty acids, sudanblack staining of cryostat sections was performed. The FLAG® epitope for the detection of both forms of the human tau proteins was stained by immunohistochemistry with M5 antibody.
Obvious histological alterations in the retinal structure of the transgenic mice were neither found in HE nor in PAS-stained paraffin sections when compared to the control. Immunohistochemistry revealed sporadic expression of transgenic tau protein in retinal ganglion cells, but sub-RPE deposits that are predominant in AMD were not detected. No apparent structural differences between 4wt1 and 4php3 mice were observed. Staining of fatty acids within the retina seemed to be slightly more intense in wildtype mice when compared to the transgenic animals.
Histopathological changes in the retina of 22 month old transgenic mice expressing forms of human tau protein were not apparent. The expression of tau protein in the retina of the transgenic mice was visible in the inner retina. This animal model lack sub-RPE deposits and might therefore not be suitable for studying AMD related retinal changes but can be used to examine AD-related retinal changes.
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