Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

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.ArticleeNeuro.4(2):e0250(2017)journal articl

Hybrid male sterility between the fresh- and brackish-water types of ninespine stickleback Pungitius pungitius (Pisces, Gasterosteidae)

Two ecologically distinct forms, fresh- and brackish-water types, of ninespine stickleback co-exist in several freshwater systems on the coast of eastern Hokkaido. Recent genetic analyses of 13 allozyme loci revealed genetic separation between the two types even though their spawning grounds were in close proximity. On the other hand, there is only a small difference in mitochondrial DNA (mtDNA) sequence between the two types suggesting that they diverged quite recently or that mtDNA introgression occurred between them. To test for postzygotic reproductive isolating mechanisms and hybrid mediated gene flow, we examined the viability and reproductive performance of reciprocal F1 hybrids. The hybrids grew to the adult size normally and both sexes expressed secondary sexual characters in the reciprocal crosses. The female hybrids were reciprocally fertile, while the male hybrids were reciprocally sterile. Histological and flow-cytometric analyses of the hybrid testis revealed that the sterility pattern was classified as `gametic sterility,' with gonads of normal size but abnormal spermatogenesis. To our knowledge, the present finding is a novel example of one sex hybrid sterility in the stickleback family (Gasterosteidae)

Histological Differentiation of Primordial Germ Cells in Zebrafish

In this study, primordial germ cells (PGCs) in zebrafish were described histologically using eosinophilic granules as a marker. PGC-like cells (PL-cells) with eosinophilic granules were identified initially at the sphere stage (4-hr postfertilization), and were observed until the bud stage, the earliest stage to which PGCs with proper morphology could be traced. The morphology and distribution of eosinophilic granules in PL-cells changed during epiboly. Mitoses of PL-cells were observed only from the shield to bud stage, after eosinophilic granules aggregated to the perinuclear region in PGCs. These shifts of eosinophilic granules corresponded histologically to those of germ plasm described in Xenopus. These results suggest that eosinophilic granules represent germ plasm in fish and that PL-cells with these granules correspond to the PGCs or presumptive PGCs (pPGCs)

Histological Comparisons of Intestines in Parasitic and Nonparasitic Lampreys, with Reference to the Speciation Hypothesis

Histological comparisons of intestinal internal structures were made for the monophyletic lamprey group comprising parasitic Lethenteron japonicum, and nonparasitic L. kessleri and the northern form of L. reissneri, in order to verify the speciation hypothesis that the nonparasitic species have been derived from a congeneric parasitic species. In the larval stage of each species, the mucosal epithelial cells were regularly arranged around an inner layer of intestine, including the typhlosole. At the metamorphosed stage, L. japonicum possessed functional mucosal folds, reflecting an adaptive change for parasitic feeding after metamorphosis. The two nonparasitic species, in which feedings are absent after metamorphosis, also exhibited mucosal folds albeit in a degenerative condition, indicating the likely presence of functional or at least rudimentary mucosal folds in an ancestral parasitic species. This finding supports a previously advocated direction of speciation in lamprey satellite species, namely nonparasitic L. kessleri and the northern form of L. reissneri speciated from ancestral stocks of parasitic L. japonicum

Germ Cell Lineage from a Single Blastomere at 8-Cell Stage in Shiro-uo (ice goby)

Shiro-uo (ice goby; teleost fish), Leucopsarion petersii, shows a unique cleavage pattern characterized by two tires of blastomeres at 8-cell stage, like that of echinoderm and amphibian embryo. Such a pattern is suitable to isolation and cell lineage experiments. In this study, cell lineage of germ-line was traced by histological observation and cell labelling experiment at the 8-cell stage. Primordial germ cells (PGCs) were first detected histologically at the 10-somite stage, and migrated to gonadal anlage at 10 days post-fertilization, through usual way described in other teleost species. When a single blastomere was labelled with tracer dye at 8-cell stage, both upper and lower tires generated labelled PGCs at gonadal anlage although upper tires occasionally. This result suggests that all blastomeres at the 8-cell stage have potential to produce PGCs in shiro-uo