Mating patterns in seminatural populations of mice influenced by MHC genotype

Because of the central role of major histocompatibility complex (MHC) genes in immune recognition, it is often assumed that parasite-driven selection maintains the unprecendented genetic diversity of these genes. But associations between MHC genotype and specific infectious diseases have been difficult to identify with a few exceptions such as Marek's disease and malaria. Alternatively, MHC-related reproductive mechanisms such as selective abortion and mating preferences could be responsible for the diversity. To determine both the nature and strength of selection operating on MHC genes by we have studied components of selection in seminatural populations of mice (Mus musculus domesticus). Here we assess MHC-related patterns of reproduction and early (preweaning) mortality by analysing 1,139 progeny born in nine populations, and 662 progeny from laboratory matings. Reproductive mechanisms, primarily mating preferences, result in 27% fewer MHC-homozygous offspring than expected from random mating. MHC genotype had no detectable influence on neonatal (preweaning) mortality. These mating preferences are strong enough to account for most of the MHC genetic diversity found in natural populations of Mus.     

Learned kin recognition cues in a social bird

In many cooperatively breeding birds, kin selection has an important role in the evolution and maintenance of social behaviour, and 'helpers' can maximize indirect fitness gains by preferentially allocating care to close relatives. Although there is evidence for kin-biased helping behaviour in several species, the mechanism of kin recognition underlying this behaviour is poorly understood. Vocalizations are the most commonly used cues in avian recognition systems, but the effectiveness of vocal signals as reliable recognition cues must depend on how they are acquired. However, there have been no experimental studies of the development of vocal recognition cues in cooperative birds; indeed, the ontogeny of all bird vocalizations other than song is poorly known in any species. Here, we show that cooperatively breeding long-tailed tits (Aegithalos caudatus) can discriminate between kin and non-kin according to the individual-specific characteristics of contact calls, and show experimentally that individuals learn these calls from provisioning adults during the nestling period. Finally, we show that the pattern of cooperative behaviour in this species is consistent with the use of recognition cues learned through association.     

MHC antigens in urine as olfactory recognition cues

The classical class I antigens of the major histocompatibility complex (MHC) are cell-surface glycoproteins which were originally discovered because they cause rapid rejection of cells or tissues grafted between unrelated individuals. These molecules are encoded by the K, D and L loci of the mouse MHC (and analogous loci in other species) which show extreme species polymorphism and a large number of alleles. In an outbreeding population 3.6 X 10(9) unique MHC class I phenotypes can be encoded by the 100 alleles at each of the K and D loci and the 6 alleles at the L locus. This level of polymorphism ensures that the cells and tissues of each unrelated individual are uniquely identified by their class I membrane-bound antigens. Like other membrane bound proteins, these class I molecules are anchored in the lipid bilayer by a hydrophobic domain encoded by exon 5. However, there have been reports of the occurrence of classical class I molecules in true solution in the blood of humans, mice, and rats. We report here that classical polymorphic class I molecules in normal rats are constitutively excreted in the urine and that untrained rats can distinguish the smell of urine samples taken from normal donors that differ only at the class I MHC locus and therefore excrete different allelomorphs of class I molecules in their urine.     

New class II-like genes in the murine MHC

Major histocompatibility complex (MHC) class I molecules present endogenous antigens to CD8+ (cytotoxic) T cells. MHC class II molecules present primarily exogenously derived antigens to CD4+ T cells. Three new genes (Ma, Mb1 and Mb2) located between the Pb and Ob genes of the murine MHC have properties indicating that they are members of the MHC class II gene family, but they are the most divergent class II members so far identified and are almost as closely related in sequence to class I genes as they are to the known class II genes.     

Invariant chain influences the immunological recognition of MHC class II molecules.

Recent experiments have implicated intracellular events in the formation of the MHC class II-peptide complexes recognized by CD4-positive T cells. These data raise the possibility that the intracellular association of class II with the non-polymorphic glycoprotein, invariant chain (Ii), may regulate the interaction between processed antigen and MHC class II molecules. To address this possibility, we have generated a series of transfected fibroblast cell lines that express class II with and without Ii. Although the presence of Ii does not seem to affect the ability of the cells to process and present intact antigen, Ii-negative cells express an altered form of class II at the cell surface. This modified conformation of class II in Ii-negative cells is detectable by an increase in the ability to present antigenic peptides to T cells and a decrease in the binding of several class II-specific monoclonal antibodies.     

Individual recognition in mice mediated by major urinary proteins.

The ability to recognize individuals is essential to many aspects of social behaviour, such as the maintenance of stable social groups, parent-offspring or mate recognition, inbreeding avoidance and the modulation of competitive relationships. Odours are a primary mediator of individuality signals among many mammals. One source of odour complexity in rodents, and possibly in humans, resides in the highly polymorphic major histocompatibility complex (MHC). The olfactory acuity of mice and rats allows them to distinguish between the urinary odours of congenic strains differing only in single genes within the MHC, although the chemical mediators or odorants are unknown. However, rodent urine also contains a class of proteins, termed major urinary proteins (MUPs), that bind and release small volatile pheromones. We have shown that the combinatorial diversity of expression of MUPs among wild mice might be as great as for MHC, and at protein concentrations a million times higher. Here we show in wild house mice (Mus domesticus) that urinary MUPs play an important role in the individual recognition mechanism.     

Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes.

Human papillomaviruses associated with cutaneous and anogenital cancers induce intraepithelial precursor lesions which may regress spontaneously or progress into invasive carcinomas. Cell-mediated immune responses are probably involved in regression of precancerous lesions and the polymorphism of the genes responsible may thus have a key role in the variability of the host response. Skin warts and cancers induced in rabbits by Shope papillomavirus provide a model to test this hypothesis. We analysed a restriction-fragment-length polymorphism of major histocompatibility complex class I and class II genes and T-cell receptor beta-chain genes in infected domestic rabbits. We found a strong linkage between wart regression and a DR alpha EcoRI fragment, and an increased relative risk of malignant transformation associated with a DQ alpha PvuII fragment. This indicates a genetic control of wart evolution, involving genes in the class II region of the major histocompatibility complex.     

HLA-restricted recognition of viral antigens in HLA transgenic mice

Cytotoxic T lymphocytes (CTL) recognize antigen in the context of the class-I products of the major histocompatibility complex (MHC). The extensive polymorphism of class-I molecules is thought to be linked to their capacity to present a large variety of foreign antigens. Whether a single T-cell receptor (TCR) recognizes two separate epitopes (the foreign antigen and an epitope on MHC molecules), or a single epitope resulting from the combination of a foreign antigen and an MHC molecule, has not yet been resolved. In view of the differences between species in primary structure of histocompatibility antigens, it might be predicted that the TCR repertoire would evolve in concert with the diversity of MHC antigens. The mouse and human TCR repertoire would be optimally adapted to engage in productive interactions only with mouse (H-2) and human (HLA) MHC antigens respectively, especially if the more conserved features of histocompatibility antigens, in addition to foreign antigen, were seen by the TCR. Alternatively, only the most variable segments of MHC antigens might be engaged in antigen presentation and thus in interaction with the TCR. In that case, interaction between MHC plus antigen and the TCR might not necessarily be limited by species-specific features. By analysis of the T-cell response against virus-infected cells in HLA-B27/human beta 2-microglobulin double transgenic mice, we report here that the mouse T-cell repertoire is perfectly capable of using the human HLA-B27 antigen as a restriction element.     

元胞自动机中斑图复制的识别算法

给出了元胞自动机中斑图复制识别的一种算法。通过定义每个元胞的特征数,将两个斑图统一放入一个区域内比较它们的特征数,从而判定是否出现复制现象。数值例子表明,该算法是有效的。     

Isolation and characterization of class I MHC genes in the giant panda (Ailuropoda melanoleuca)

Artificial breeding is an important project to protect,recover and reintroduce endangered species.Knowledge of the population’s genetic diversity at functional loci is important for the establishment of effective captive breeding programs.The major histocompatibility complex(MHC) genes are ideal candidate genetic markers to inform planned breeding,due to their high levels of polymorphism and importance in the main immune coding region of the vertebrate genome.In this study,we constructed BAC-based contigs and isolated six functional MHC class Ⅰ genes from the giant panda(Ailuropoda melanoleuca),which we designated Aime-C,Aime-F,Aime-I,Aime-K,Aime-L and Aime-1906.Analyses of the tissue expression patterns and full-length cDNA sequences of these class I genes revealed that Aime-C,-F,-I and-L could be considered classical class Ⅰ loci,due to their extensive expression patterns and normal exonic structures.In contrast,Aime-K and-1906 appeared to be nonclassical genes based on their tissue-specific expression patterns and the presence of an abnormal exon 7 in both genes.We established techniques for genotyping exons 2 and 3 of the classical loci using locus-specific single strand conformation polymorphism(SSCP) and sequence analysis.In the Chengdu captive population,we identified one monomorphic locus(Aime-F) and three polymorphic loci with different numbers of alleles(4/4/4 exon 2 alleles at Aime-C/I/L and 6/5/5 exon 3 alleles at Aime-C/I/L).The distributions of the Aime-C,-I and-L alleles among members of different families were in good agreement with the known pedigree relationships,suggesting that the genotyping results are reliable.Therefore,the MHC-I genotyping techniques established in this study may provide a powerful tool for the future design of scientific breeding or release/reintroduction programs.     

Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice.

T cells that recognize self antigen are clonally deleted in the thymus--a maturation process that occurs in the context of histocompatibility molecules and the T-cell receptor. The minor lymphocyte stimulation antigens (Mls) effect these deletions through interactions with the V beta portion of the T-cell receptor, thus mimicking bacterial 'superantigens'. Intrigued by the fact that each known Mls gene maps to the same chromosomal region as an endogenous mouse mammary tumour virus (Mtv), we reevaluated the linkage relationships between the two gene families. Here we report perfect concordance in inbred and recombinant inbred mice between the presence of four Mtv proviruses with the expression of Mls gene products. These data suggest a general model in which mammary tumour virus gene products themselves are the ligands that shape a considerable portion of the immunological repertoire of common laboratory mice.     

T-cell tolerance by clonal anergy in transgenic mice with nonlymphoid expression of MHC class II I-E

T-cell reactivity to the class II major histocompatibility complex I-E antigen is associated with T-cell antigen receptors containing the V beta gene segments V beta 17a and V beta 5. Mice expressing I-E with the normal tissue distribution (on B cells, macrophages, dendritic cells and thymic epithelium) induce tolerance to self I-E by clonal deletion in the thymus. By contrast, we find that transgenic INS-I-E mice that express I-E on pancreatic beta-cells, but not in the thymus or peripheral lymphoid organs, are tolerant to I-E but have not deleted V beta 5- and V beta 17a-bearing T cells. Moreover, whereas T-cell populations from nontransgenic mice proliferate in response to receptor crosslinking with V beta 5- and V beta 17a-specific antibodies, T cells from INS-I-E mice do not. Thus, our experiments provide direct evidence that T-cell tolerance by clonal paralysis does occur during normal T-cell development in vivo.     

Defining brain wiring patterns and mechanisms through gene trapping in mice

The search to understand the mechanisms regulating brain wiring has relied on biochemical purification approaches in vertebrates and genetic approaches in invertebrates to identify molecular cues and receptors for axon guidance. Here we describe a phenotype-based gene-trap screen in mice designed for the large-scale identification of genes controlling the formation of the trillions of connections in the mammalian brain. The method incorporates an axonal marker, which helps to identify cell-autonomous mechanisms in axon guidance, and has generated a resource of mouse lines with striking patterns of axonal labelling, which facilitates analysis of the normal wiring diagram of the brain. Studies of two of these mouse lines have identified an in vivo guidance function for a vertebrate transmembrane semaphorin, Sema6A, and have helped re-evaluate that of the Eph receptor EphA4.     

白血病小鼠模型中P53、C-myc基因表达的变化研究

探讨DNA、RNA病毒诱导小鼠发生白血病的机制。用单纯疱疹病毒Ⅱ型（HSV－2）和C型RNA病毒诱导70只昆明小鼠，光学显微镜检测HSV－2、C型病毒诱导发生白血病的成功率。正常对照组为30只昆明小鼠。免疫组化法检测HSV－2、C型病毒致瘤后P^53、G－myc基因表达的变化。70只昆明小鼠中有47只发生白血病，成功率为67．1％。47只白血病小鼠P^53、C－myc蛋白阳性表达率均比正常对照组高（P＜0．05）；23只未形成白血病的实验组小鼠P^53、C－myc蛋白阳笥表达率均与正常对照组无显差异（P＞0．05）。HSV－2、C型病毒可以通过调节P^53、C－myc基因的表达从而诱导小鼠白血病的发生。