Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we “clone” the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc(HSA21q;MAC)1Yakaz (“TcMAC21”). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.

The synthesis of a Pt-and Pd-nanoparticle-dispersed polyimide film as a precursor for the preparation of a metal-doped carbon molecular sieve (CMS) membrane for hydrogen separation has been performed. Impregnation of Pt(II) acetylacetonate and Pd(II) acetylacetonate dissolved in supercritical CO 2 yielded Pt and Pd nanoparticles (diameters 12 and 5 nm, respectively) that were highly dispersed inside polyimide films under optimized conditions. The impregnation temperature and varieties of polyimide films strongly influenced the dispersion of the metal particles. The Pd-doped CMS membrane was successfully prepared from the polyimide and Pd(II) acetylacetonate composite. It showed good hydrogen separation performance.

We describe two recessive alleles of a rice heterochronic gene, plastochron1-1 (pla1-1) and pla1-2, that reduce the length of the plastochron to approximately half that of the wild type. Because the onset of the reproductive phase in pla1 was not temporally affected, the number of leaves produced in the vegetative phase was nearly twice that produced in the wild type. Panicle development was severely disturbed in pla1 mutants. In pla1-1, many primordia of primary rachis branches were converted into vegetative shoots. These ectopic shoots repeated the initiation of panicle development and the conversion of primary rachis branches into shoots. In the weak allele pla1-2, however, only the basal one or two primordia developed as vegetative shoots, and the remaining primordia developed to produce a truncated panicle. These results indicate that both vegetative and reproductive programs are expressed simultaneously during the reproductive phase of pla1; however, the degree varied depending on the strength of the allele. Accordingly, pla1 is a heterochronic mutation that extends the vegetative period. The shoot apical meristem of pla1 was larger than that of the wild type, although the shape was not modified. An in situ hybridization experiment using the histone H4 gene as a probe revealed that cell divisions are accelerated in the pla1 meristem. The PLA1 gene is considered to regulate the duration of the vegetative phase by controlling the rate of leaf production in the meristem.

We describe two recessive alleles of a rice heterochronic gene, plastochron1-1 ( pla1-1 ) and pla1-2 , that reduce the length of the plastochron to approximately half that of the wild type. Because the onset of the reproductive phase in pla1 was not temporally affected, the number of leaves produced in the vegetative phase was nearly twice that produced in the wild type. Panicle development was severely disturbed in pla1 mutants. In pla1-1 , many primordia of primary rachis branches were converted into vegetative shoots. These ectopic shoots repeated the initiation of panicle development and the conversion of primary rachis branches into shoots. In the weak allele pla1-2 , however, only the basal one or two primordia developed as vegetative shoots, and the remaining primordia developed to produce a truncated panicle. These results indicate that both vegetative and reproductive programs are expressed simultaneously during the reproductive phase of pla1 ; however, the degree varied depending on the strength of the allele. Accordingly, pla1 is a heterochronic mutation that extends the vegetative period. The shoot apical meristem of pla1 was larger than that of the wild type, although the shape was not modified. An in situ hybridization experiment using the histone H4 gene as a probe revealed that cell divisions are accelerated in the pla1 meristem. The PLA1 gene is considered to regulate the duration of the vegetative phase by controlling the rate of leaf production in the meristem. INTRODUCTIONPlant development generally is divided into four distinct phases: embryogenesis, early vegetative phase (juvenile phase), late vegetative phase (adult phase), and reproductive phase (Conway and Poethig, 1993). In almost all plant species, two phase changes are recognized easily by the distinct morphological changes that occur in plants from the embryonic phase to the juvenile vegetative phase and from the adult vegetative phase to the reproductive phase. A clear change between the juvenile and adult vegetative phases has been reported for English ivy, maize, and Arabidopsis (Hackett, 1985;Zimmerman et al., 1985;Poethig, 1988Poethig, , 1990 Lawson and Poethig, 1995;Telfer et al., 1997). However, in several species including rice, the phase change from juvenile to adult is not clear because it is continuous and is not accompanied by gross visible changes.Whatever the case may be, the plant life cycle is driven by phase-specific genetic programs that are partially overlapping (Bongard-Pierce et al., 1996). Mutations that delay or advance phase change have been reported for several plant species. Late-flowering mutants can be interpreted as prolonging the vegetative phase and delaying the reproductive phase. Recently, using trichome distribution or epidermal characters as phase-specific markers, researchers have described several late-flowering and dwarf mutations that prolong the juvenile phase (Evans and Poethig, 1995;Telfer et al., 1997).Heterochronic mutations affecting the timing of developmental events may be of major sig...

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Macrophage migration inhibitory factor (MIF) has been rediscovered as a proinflammatory cytokine, pituitary hormone, and glucocorticoid-induced immunoregulator. We have recently identified the expression of MIF in adipocytes and found that tumor necrosis factor (TNF)-alpha stimulates its secretion from 3T3-L1 adipocytes. Since adipocytes are regarded as a potential source of various biologically active substances, we examined in more detail the effect of TNF-alpha on MIF expression in 3T3-L1 adipocytes in the present study. We found that TNF-alpha induced MIF mRNA in dose- and time-dependent manners. After stimulation with TNF-alpha, the amount of intracellular MIF protein was unchanged or slightly decreased, concomitant with increased release of this protein into the extracellular space. This observation indicates that TNF-alpha stimulates MIF secretion from the constitutively expressed intracellular pool of 3T3-L1 adipocytes and promotes de novo synthesis of MIF. From evaluation of the mechanism of MIF gene expression, we found that tyrosine kinase inhibitors, either genistein or herbimycin A, suppressed the MIF mRNA induction by TNF-alpha. The results suggest the possibility that upregulation of MIF mRNA expression by TNF-alpha is mediated by a tyrosine kinase-dependent pathway. Taken together, the present observations shed light on the role of MIF in the metabolism of obesity and diabetes.