Retinal degeneration and rd1 mutation in NC/Tnd mice-a human atopic dermatitis model.

Kaoru Karasawa, Akane Tanaka, Kyungsook Jung, Akira Matsuda, Noriko Okamoto, Kumiko Oida, Nobuyuki Ebihara, Keitaro Ohmori, Hiroshi Matsuda

Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Graduate School, Institute of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.

Current eye research 2011 Apr

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NC/Tnd mice, a spontaneous model for human atopic dermatitis, are also useful animal models for various corneal disorders accompanying allergic diseases. The purposes of the current study were to investigate the development of retinal degeneration in NC/Tnd mice. Histological examination was performed to determine time-dependent alterations of the retina in NC/Tnd from 8 to 28 days of age. Apoptotic cells were determined by TUNEL assay. Retinal function was examined by electroretinography. Fundoscopy was performed in NC/Tnd mice at 8 weeks of age. Melanin contents in whole-eye extracts were measured by spectrophotometry. Since the retinal degeneration 1 (rd1) mutation in the rod photoreceptor cyclic guanosine monophosphate phosphodiesterase 6 β-subunit (Pde6b(rd1)) has been identified in laboratory mice, the possible existence of the rd1 mutation was analyzed with PCR genotyping and gene sequencing. C57BL/6, WB, and C3H/HeN mice were used as controls. Histological examination revealed rapid postnatal retinal degeneration in NC/Tnd mice. The number of apoptotic cells in the outer nuclear layer (ONL) increased with aging, and finally the ONL disappeared. Histological abnormality was not obvious in the inner nuclear layer or the ganglion cell layer. Electroretinography shows no response in adult NC/Tnd mice. Fundoscopic observation revealed hypopigmentation in the retina, and melanin contents in the eye were significantly reduced when compared with other inbred strains. Insertion in the rd1 allele was confirmed and a nonsense mutation of Pde6b(rd1) gene was determined in NC/Tnd mice. NC/Tnd mice also preserve the Pde6b(rd1) gene mutation resulting in the rapid postnatal retinal degeneration similar to that in C3H/HeN mice. Unlike C3H/HeN mice, since melanin contents of the retina in NC/Tnd mice was decreased, unknown defects may be present in the process of melanin composition in retinal pigment epithelial cells during fetal development of NC/Tnd mice.

Citation

Kaoru Karasawa, Akane Tanaka, Kyungsook Jung, Akira Matsuda, Noriko Okamoto, Kumiko Oida, Nobuyuki Ebihara, Keitaro Ohmori, Hiroshi Matsuda. Retinal degeneration and rd1 mutation in NC/Tnd mice-a human atopic dermatitis model. Current eye research. 2011 Apr;36(4):350-7