Inversion in the H-2 complex of t-haplotypes in mice

Mouse t-haplotypes demonstrate strong linkage disequilibrium between t-lethal genes and specific H-2 types, presumably a result of recombination suppression between t and normal chromosomes. The observation of free recombination occurring between two complementary t-haplotypes suggested a chromosomal mismatch between t and normal chromosomes. Recent data showing the H-2 complex to be misplaced relative to two other markers, T and tf, in t-haplotypes suggested that chromosomal rearrangement in t-haplotypes might be the basis for their 'mismatch' with the normal chromosome. Here, to analyse the molecular nature of the rearrangement, we have cloned a polymorphic H-2 class I restriction fragment, which had previously been shown to map centromeric to the serologically defined H-2 complex in t-haplotypes. Genetic mapping studies show that this cloned t-DNA is homologous to the H-2 D region of wild-type chromosomes, and that the E alpha Ia gene maps telomeric to this DNA fragment in t-haplotypes, in contrast to its orientation in wild-type chromosomes. These results give molecular evidence for an inversion of H-2 in t-haplotypes, which may be at least partially responsible for recombination suppression and thus for linkage disequilibrium.     

Control of the sperm-oocyte switch in Caenorhabditis elegans hermaphrodites by the fem-3 3' untranslated region.

In the Caenorhabditis elegans hermaphrodite germ line, sperm and then oocytes are made from a common pool of germ-cell precursors. The decision to differentiate as a sperm or an oocyte is regulated by the sex-determining gene, fem-3. Expression of fem-3 in the hermaphrodite germ line directs spermatogenesis and must be negatively regulated to allow the switch to oogenesis. In adult hermaphrodites (which are producing oocytes), most fem-3 RNA is found in the germ line, consistent with both the requirement for fem-3 in hermaphrodite spermatogenesis and the maternal effects of fem-3 on embryonic sex determination. Whereas loss-of-function mutants in fem-3 produce only oocytes, hermaphrodites carrying any of nine fem-3 gain-of-function (gf) mutations make none; instead sperm are produced continuously and in vast excess over wild-type amounts. Genetic analyses suggest that fem-3(gf) mutations have escaped a negative control required for the switch to oogenesis. Here we report that all nine fem-3(gf) mutants carry sequence alterations in the fem-3 3' untranslated region (3' UTR). There is no increase in the steady-state level of fem-3(gf) RNA over wild-type, but there is an increase in the polyadenylation of fem-3(gf) RNA that is coincident with the unregulated fem-3 activity. Results of a titration experiment support the hypothesis that a regulatory factor may bind the fem-3 3' UTR. We speculate that fem-3 RNA is regulated through its 3' UTR by binding a factor that inhibits translation, and discuss the idea that this control may be part of a more general regulation of maternal RNAs.     

Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection

H-2 gene transfection was used to restore expression of H-2K antigens in metastatic and non-metastatic subclones of a murine fibrosarcoma that lack their major histocompatibility complex-encoded H-2K antigens. De novo expression of H-2K reduced tumorigenicity and abolished the formation of metastasis in syngeneic mice. Expression of H-2K may lead to effective recognition of the disseminating tumour cells by the host immune system.     

Structural polymorphism of I-E subregion antigens determined by a gene in the H-2K to I-B genetic interval

THE generation of immune responses in mice is influenced by Ir genes located in the I region of the major histocompatibility complex (MHC)(1). In some instances maximum responses require complementation by two genes, one in the I-A or I-B and the other in the I-E or I-C subregion(2,3). The effects of these genes are thought to be mediated by Ia alloantigens, which are cell surface molecules whose expression is controlled by the I region(4). This is based on the observations that anti-Ia sera inhibit in vitro immune responses(5,6), and soluble factors that enhance in vitro immune responses express Ia alloantigenic determinants(7,9). Jones et al.(10), using two-dimensional gel electrophoresis, observed that the expression of I-E subregion antigens is controlled by two genes, one in the I-A subregion, the other in the I-E subregion, and that the polymorphism of these antigens is influenced by an I-A subregion gene. As an explanation, the authors proposed that only one of the two polypeptide chains present in I-E immunoprecipitates is an I-E subregion product, the second being a product of the I-A subregion. Antisera obtained by cross-immunisation of I-E subregion-disparate strains of mice immunoprecipitates a molecular complex consisting of two chains, designated alpha and beta, with molecular weights of 32,000 and 29,000 respectively(11-14). Previous studies suggested that I-E antigens isolated from B10.A(5R) and B10.D2 mice had identical alpha-chains but different (beta)-chains(15). However, as these mice differed at multiple genetic regions, it was not possible to show which I subregion(s) determined the polymorphism of the E(beta) chain. Therefore, we investigated the effects of the I-A subregion on the polymorphism of I-E subregion antigens. We have now shown by peptide mapping that the I-E subregion polymorphism which Jones et al. found to be controlled by the I-A subregion probably reflects structural polymorphism of beta-chains controlled by an I-A subregion gene.     

MyHC基因在C2C12成肌细胞分化过程中的时序表达

以体外培养的C2C12成肌细胞为研究对象,然后利用荧光定量PCR检测肌球蛋白重链(myosin heavy chains,MyHC)的3种亚型MyHC1、MyHC2x和MyHC2b在成肌诱导分化中(0-8 d)中的时序表达规律.结果表明,MyHC1基因在诱导分化的0-4 d表达呈上升趋势,4-8 d又呈下降趋势,在第4 d和第6 d的表达水平显著高于其他天数(p0.05).MyHC2x基因在诱导分化的0-6 d表达呈上升趋势,但在第8 d又开始下降.MyHC2b在诱导分化的0-8 d中表达一直呈上升趋势,第6 d和第8 d表达水平显著高于其他天数(p0.05).     

The gene encoding the Ia antigen-associated invariant chain (Ii) is not linked to the H-2 complex

The invariant (Ii) chain of murine Ia antigens is associated with the intracellular but not the cell-surface forms of the A alpha:A beta and E alpha:E beta Ia complexes. Due to its unique subcellular localization, Ii has been postulated to play a part in the assembly or intracellular transport of the Ia alpha:beta complexes, which function in immune recognition. A more general role for Ii in the transport of other cell proteins has also been suggested. Because of the unusual subunit composition of Ia antigens and because the synthesis of alpha, beta and Ii chains is coordinately regulated, it was of interest to determine whether, like the alpha and beta chains, Ii is encoded by a gene in the I region of the H-2 histocompatibility complex. We report here the use of an Ii chain polymorphism present in Mus spretus to demonstrate that the gene for Ii is not linked to the H-2 complex. Thus, intracellular Ia antigens consist of the products of two linked genes and one unlinked gene.     

C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains.

The induction of the hermaphrodite vulva and the migration of the sex myoblasts in the nematode Caenorhabditis elegans are both controlled by intercellular signalling. The gonadal anchor cell induces formation of the vulva from nearby hypodermal cells, and a set of somatic gonadal cells attract the migrating sex myoblasts to their final positions. Many genes required for vulval induction have been identified, including the let-23 receptor tyrosine kinase gene and the let-60 ras gene. We report here the identification and characterization of a new gene, sem-5 (sem, sex muscle abnormal), that acts both in vulval induction and in sex myoblast migration. On the basis of its DNA sequence, sem-5 encodes a novel 228-amino-acid protein which consists almost entirely of one SH2 (SH, src homology region) and two SH3 domains. SH2 and SH3 domains are present in many signalling proteins regulated by receptor and non-receptor tyrosine kinases. Mutations that impair sem-5 activity alter residues that are highly conserved among different SH2 and SH3 domains. Our results indicate that the sem-5 gene encodes a novel protein that functions in at least two distinct cell-signalling processes.     

表面对氢负离子在梯度电场中光剥离的调控研究

利用闭合轨道理论对氢负离子体系在梯度电场和弹性表面附近的光剥离进行了研究,重点探讨了弹性表面对氢负离子在梯度电场中光剥离截面的影响.研究结果表明,氢负离子体系在梯度电场和弹性表面附近的光剥离与弹性表面的位置有关.当弹性表面距离氢负离子的距离比较远时,弹性表面对光剥离截面的影响较小,光剥离截面和只有梯度电场时的截面基本吻合;但是随着弹性表面到氢负离子距离的减小,弹性表面的影响越来越明显,光剥离截面的振荡振幅越来越大.除此之外,我们还对弹性表面位于Z0的空间和位于Z0的空间的情况进行了比较.结果表明,当弹性表面到氢负离子之间的距离给定时,弹性表面位于Z0的空间时的光剥离截面的振荡要比位于Z0的空间的情况要复杂.因此,我们可以通过调整弹性表面的位置对氢负离子在梯度电场中的光剥离进行调控研究.本文的研究对于理解负离子体系在非匀强电场和表面附近的光剥离可以提供一定的参考价值.