Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases.

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Guiana chestnut is a perennial tropical plant that has recently become popular as a potted ornamental in Japan. In October 2001, severe stem rot occurred on Guiana chestnut plants grown in a greenhouse in Mie Prefecture, Japan. Water-soaked lesions appeared initially at the base of the stems and enlarged gradually toward the tops of plants. The affected tissues were softened and turned dark brown. Rotting was observed in the vascular bundles with advanced disease development. Globose hyphal swellings were numerous on diseased stems. Sections from diseased stems were cleaned by washing with running tap-water, placed on water agar, and incubated at 25°C. A species of Pythium was identified on the basis of morphological and cultural characteristics (1) and isolated consistently from the rotted stems of diseased plants. All isolates produced abundant hyphal swellings that were globose, smooth, 12 to 39 μm in diameter, mostly terminal, dark colored, and with dense granulated contents. Zoospores were absent. All isolates were of the compatibility ‘+ type’ with production of sexual organs when paired with cultures of the ‘- type’ tester isolate of Pythium splendens Braun (CBS462.48). Oogonia produced by crossings between Guiana chestnut isolates and isolate CBS462.48 were terminal or intercalary, globose, smooth-walled, and 32 to 38 μm in diameter. Antheridia were terminal, one to three per oogonium, sac-like, and diclinous. Oospores were single, aplerotic, globose, and 28 to 32 μm in diameter. The thickness of the oospore wall ranged from 1 to 2 μm. The internal transcribed spacer rDNA sequences of representative isolate OPU591 from Guiana chestnut matched those of CBS462.48 (similarity 99.2%) and have been deposited in GenBank under the Accession No. AY375242. Pathogenicity tests were conducted on potted Guiana chestnut plants (30 cm high and 7 to 10 cm in diameter at base of the stem) using isolate OPU591. A mycelial suspension from one culture, grown at 25°C for 7 days on water agar, was inoculated onto a single plant. Prior to inoculation, a wound (10 mm deep and 30 mm long) was made on the surface at the stem base on five plants. The mycelial suspension was poured onto the base of the stems of five wounded and five nonwounded plants. In addition, five wounded and five nonwounded, noninoculated plants were used as controls. Plants were maintained in a greenhouse for 8 weeks after inoculation. The temperature and relative humidity in the greenhouse ranged from 25 to 30°C and 65 to 75%, respectively. Dark-brown rotting developed on the stems of all wounded, inoculated plants by 20 days after inoculation. P. splendens was isolated from diseased tissues and found to be morphologically identical to the original isolate. This confirmed P. splendens as the causal agent of the disease. Disease did not develop on nonwounded inoculated plants or noninoculated plants. To our knowledge, this is the first report of P. splendens on Guiana chestnut. Potted plants of Guiana chestnut are often injured by frequent transplanting and transferring. Such injuries may have predisposed the plant to infection by P. splendens. Reference: (1) A. J. van der Plaats-Niterink. Page 1 in: Monograph of the Genus Pythium. Studies in Mycology Vol. 21, Centraalbureau Voor Schimmelcultures, Baarn, the Netherlands, 1981.

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