Immune presensitization and local intrauterine defences as determinants of success or failure of murine interspecies pregnancies

Putatively immuno-incompetent Mus musculus females exhibited failure to support pregnancy of Mus caroli embryos. These results for M. musculus females (i.e. treated by cyclosporine A, of the nu/nu genotype, and as an interspecies chimaera) can be explained in immunological terms. Mus musculus females possessed pre-sensitized cytotoxic T cells against Mus caroli antigen. Nu/nu mice possessed activated NK cells and macrophages, and selectively discriminated against Mus caroli embryos early in pregnancy unlike normal +/+ females; the requirement for T cells to activate non-specific cytotoxic effector mechanisms was bypassed in nu/nu mice. Mus caroli are not inbred, and interspecies chimaeras which are tolerant of the antigens on the Mus musculus donor strain were not tolerant of cells from unrelated Mus caroli. Interspecies chimaeras also behaved as if they were pre-sensitized to Mus caroli. Our results show that Mus caroli embryos recruit fewer active suppressor cells even when gestating in Mus caroli decidua as compared to Mus musculus embryos in Mus musculus decidua and that the ability of Mus caroli placental cells to directly inhibit cytotoxic effector cell killing was inherently less than the inhibitory activity of placental cells from Mus musculus. Mus caroli embryos therefore appear to be less well defended against maternal immune attack even when gestating in a uterus possessing compatible Mus caroli decidual tissue.     

小家鼠和实验小鼠遗传特性的比较研究

本文用同工酶电泳法、微量细胞毒法和免疫双向扩散法对我国4个动物地理区的6个采集点的156个小家鼠(Mus musculus)进行了遗传特性的调查。结果发现:在全部被测的13个位点中,小家鼠在7个位点上存在着多种实验小鼠中罕见的基因组成;而不同动物地理区和亚区的小家鼠的遗传特性又各不相同。从而指出将小家鼠的特有基因导入实验小鼠,培育新品系的重大意义。     

The diverse origins of New Zealand house mice

Molecular markers and morphological characters can help infer the colonization history of organisms. A combination of mitochondrial (mt) D-loop DNA sequences, nuclear DNA data, external measurements and skull characteristics shows that house mice (Mus musculus) in New Zealand and its outlying islands are descended from very diverse sources. The predominant genome is Mus musculus domesticus (from western Europe), but Mus musculus musculus (from central Europe) and Mus musculus castaneus (from southern Asia) are also represented genetically. These subspecies have hybridized to produce combinations of musculus and domesticus nuclear DNA coupled with domesticus mtDNA, and castaneus or musculus mtDNA with domesticus nuclear DNA. The majority of the mice with domesticus mtDNA that we sampled had D-loop sequences identical to two haplotypes common in Britain. This is consistent with long-term British-New Zealand cultural linkages. The origins of the castaneus mtDNA sequences widespread in New Zealand are less easy to identify.     

Diverse wild mouse origins of xenotropic, mink cell focus-forming, and two types of ecotropic proviral genes

We analyzed wild mouse DNAs for the number and type of proviral genes related to the env sequences of various murine leukemia viruses (MuLVs). Only Mus species closely related to laboratory mice carried these retroviral sequences, and the different subclasses of viral env genes tended to be restricted to specific taxonomic groups. Only Mus musculus molossinus carried proviral genes which cross-reacted with the inbred mouse ecotropic MuLV env gene. The ecotropic viral env sequence associated with the Fv-4 resistance gene was found in the Asian mice M. musculus molossinus and Mus musculus castaneus and in California mice from Lake Casitas (LC). Both M. musculus castaneus and LC mice carried many additional Fv-4 env-related proviruses, two of which are common to both mouse populations, which suggests that these mice share a recent common ancestry. Xenotropic and mink cell focus-forming (MCF) virus env sequences were more widely dispersed in wild mice than the ecotropic viral env genes, which suggests that nonecotropic MuLVs were integrated into the Mus germ line at an earlier date. Xenotropic MuLVs represented the major component of MuLV env-reactive genes in Asian and eastern European mice classified as M. musculus molossinus, M. musculus castaneus, and Mus musculus musculus, whereas Mus musculus domesticus from western Europe, the Mediterranean, and North America contained almost exclusively MCF virus env copies. M. musculus musculus mice from central Europe trapped near the M. musculus domesticus/M. musculus musculus hybrid zone carried multiple copies of both types of env genes. LC mice also carried both xenotropic and MCF viral env genes, which is consistent with the above conclusion that they represent natural hybrids of M. musculus domesticus and M. musculus castaneus.     

Serological survey of complement factor H in common laboratory and wild mice: a new third allotype

Antigenic specificities of complement factor H from mice were studied serologically. In addition to previously reported allotypes, referred to as H.1 and H.2, a new allotype of complement factor H, H.3, was identified in the BFM/2Ms strain derived from European wild mice. Using three different alloantisera raised against the various mouse factor H allotype, a serological survey of the common laboratory strains and wild-derived strains of Mus musculus and its relatives, Mus spretus, Mus spretoides, and Mus spicilegus was carried out. All of the common laboratory strains examined in this survey had the H.1 allotype except for STR/N which had H.2. The geographical distributions of factor H allotypes in M. musculus were specific to the subspecies. Mice derived from Mus musculus domesticus and Mus musculus castaneus had the H.1 allotype. Mice derived from M. m. musculus, Mus musculus bactrianus, and Mus musculus molossinus had the H.2 allotype. Only BFM/2Ms and BFM/1Mpl strains derived from M. m. domesticus had the novel H.3 allotype. Sera of mice from strains derived from M. spretoides and M. spicilegus cross-reacted with H.2-specific antiserum, and those from M. spretus cross-reacted with H.3-specific antiserum.     

Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels

Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived strain A/J, and the Mus musculus castaneus derived strain CAST/Ei. We describe approaches for the accurate identification of nucleotide and structural variation in the genomes of vertebrate experimental organisms, and show how these techniques can be applied to help prioritize candidate genes within quantitative trait loci.     

Reduced nucleotide variability at an androgen-binding protein locus (Abpa) in house mice: evidence for positive natural selection.

Previous work has shown that the gene for the alpha subunit of androgen-binding protein, Abpa, may be involved in premating isolation between different subspecies of the house mouse, Mus musculus. We investigated patterns of DNA sequence variation at Abpa within and between species of mice to test several predictions of a model of neutral molecular evolution. Intraspecific variation among 10 Mus musculus domesticus alleles was compared with divergence between M. m. domesticus and M. caroli for Abpa and two X-linked genes, Glra2 and Amg. No variation was observed at Abpa within M. m. domesticus. The ratio of polymorphism to divergence was significantly lower at Abpa than at Glra2 and Amg, despite the fact that all three genes experience similar rates of recombination. Interspecific comparisons among M. m. domesticus, Mus musculus musculus, Mus musculus castaneus, Mus spretus, Mus spicilegus, and Mus caroli revealed that the ratio of nonsynonymous substitutions to synonymous substitutions on a per-site basis (Ka/Ks) was generally greater than one. The combined observations of no variation at Abpa within M. m: domesticus and uniformly high Ka/Ks values between species suggest that positive directional selection has acted recently at this locus.     

Altered Turnover of Hypoxanthine Phosphoribosyltransferase in Erythroid Cells of Mice Expressing Hprt a and Hprt b Alleles

We have previously shown that mice expressing Hprt a allele(s) have erythrocyte hypoxanthine phosphoribosyltransferase (HPRT) levels that are approximately 25-fold (Mus musculus castaneus) and 70-fold (Mus spretus) higher than in mice that express the Hprt b allele (Mus musculus domesticus; C57BI/6J; C3H/HeHa), and that these differences in erythrocyte HPRT levels are due to differences in the turnover rates of the HPRT A and B proteins as reticulocytes mature to erythrocytes. We show here that: the taxonomic subgroups of the genus Mus are essentially monomorphic for the occurrence of either the Hprt a or the Hprt b allele, with Hprt a being common in the aboriginal species (M. spretus, Mus hortulanus and Mus abbotti) and in several commensal species (Mus musculus musculus, M. m. castaneus, Mus musculus molossinus), while Hprt b is common in feral M. m. domesticus populations as well as in all inbred strains of mice tested; in all these diverse Mus subgroups there is a strict association of Hprt a with high and Hprt b with low levels of erythrocyte HPRT; and, the association between the occurrence of the Hprt a allele and elevated erythrocyte HPRT levels is retained following repeated backcrosses of wild-derived Hprt a allele(s) into the genetic background of inbred strains of mice with the Hprt b allele. Collectively, these observations indicate that the elevated and low levels of erythrocyte HPRT are specified by differences in the Hprt a and b structural genes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Polymorphism of C lambda genes and units of duplication in the genus Mus

The number of Ig C lambda genes in nine geographically widespread species from the four subgenera in the genus Mus was estimated from the number of Bam HI and Eco RI restriction fragments that hybridize under high stringency conditions to cDNA probes of BALB/c inbred mouse origin (Mus musculus domesticus). Three closely related species in the subgenus Mus, M. musculus, M. spretus, and M. spicelegus, show considerable variation in the number of C lambda genes. Estimates of gene numbers in these animals range from two C lambda genes in M. spretus from Puerto Real, Spain to 12 C lambda genes in M. musculus musculus from Studenec, Czechoslovakia. Strains of mice carrying either six or 10 C lambda genes were derived from a single population of M. musculus domesticus from Centreville, MD. The hybridization patterns of mice exhibiting C lambda gene amplification indicate that duplications are of relatively recent origin and probably occurred by reiteration of a DNA segment closely related to the 6.5 kb [C lambda 3 - C lambda 1] unit found in BALB/c inbred mice. Three more distantly related species in the subgenus Mus, and a species representing the Nannomys subgenus all appear to carry only four C lambda genes. DNA of species representing the Coelomys and Pyromys subgenera hybridized weakly to the C lambda cDNA probes, but these animals also have no more than four C lambda genes. Thus, there may be a base number of four C lambda genes in most species in the genus Mus. All inbred strains of mice so far examined also have only four C lambda genes, but no feral M. musculus examined have fewer than six C lambda genes. One explanation of the discrepancy in the number of genes between inbred and feral M. musculus is that C lambda genes were deleted during the process of inbreeding.     

苦参碱的提取分离及对小鼠的毒性研究

采用酸性乙醇提取、乙醚萃取、硅胶柱层析分离等方法从苦参中分离到苦参碱单体.以小鼠为实验动物进行毒性测定,小鼠的死亡主要集中在48h内,48h后无小鼠的死亡现象.小鼠对苦参碱的耐受量大于30mg.k-g1,小于140mg.k-g1,致死中量LD50为64.01mg.kg-1,回归方程Y=-3.2370+4.5602X,LD50标准误差SE=6.14.适口性的测定表明,苦参碱对小鼠有较好的适口性,可以作为杀鼠剂使用.     

Hemoglobin and oxygen: different affinities in two species of rodents (Mus musculus and Pitymys duodecimcostatus)

Five different hemoglobins have been demonstrated by polyacrylamide-gel disk electrophoresis in the species Mus musculus. Oxygen affinities of hemoglobin (P50) from Mus musculus and Pitymys duodecimcostatus hemolysates were determined at pH 7.4 and 37 degrees C. Values obtained for delta log P50/delta pH in hemolysates from both species point out a more pronounced Bohr effect in Pitymys duodecimcostatus.     

Biosystematic study of mice of the genus Mus: karyotype and electrophoretic analysis of total proteins

Two forms of sympatric mice are captured in North - Tunisia: long - tailed mouse and short - tailed mouse. They are often considered as two semi - species of genus Mus, respectively Mus musculus musculus et Mus musculus spretus. They have the same Karyotype (2n = acrocentrics). The electrophoretic study of total proteins, shows up genetics differences. These two forms of mice may be considered as two different species, as like as mices of Europe: Mus musculus at long-tailed and Mus spretus at short tailed.     

Effects of alterations in the immunocompetent status of Mus musculus females on the survival of transferred Mus caroli embryos

The role of the immune system in promoting the midterm death of Mus caroli embryos transferred to the Mus musculus uterus was studied in vivo by transferring M. caroli blastocysts to recipients with altered immune status. Transfers of embryos to chimaeric mothers (Mus musculus in equilibrium Mus caroli), which were expected to be tolerant of species antigens, resulted in survival of M. musculus embryos but death of M. caroli embryos. The preferential survival of M. musculus embryos was explained by showing that M. musculus embryos can survive in the M. caroli uterus. Transfers to T cell-deficient mice of genotype nu/nu and to NK cell-deficient mice of genotype bg/bg as well as treatment of normal transfer recipients with Cyclosporin A or anti-Ia antiserum failed to prolong survival. However, immunization of recipients with M. caroli lymphocytes promoted more rapid and uniform failure of the interspecies pregnancy. Cytotoxic cells were detected in the resorbing embryos on Day 10.5 in immune pregnancies and on Day 12.5 in non-immune pregnancies and these cells were promiscuous in their pattern of lysis, showing equal reactivity against M. caroli, transfer recipient and 3rd party target cells. These experiments show that failure of M. caroli embryos in the M. musculus uterus is complex, but probably does not involve responses by classical cytotoxic T lymphocyte or natural killer cell pathways. Participation of the immune system in the resorption process, however, is confirmed and is associated with generation of promiscuous cytolytic cells.     

Genetics of intracisternal-A-particle-related envelope-encoding proviral elements in mice.

Intracisternal-A-particle-related envelope-encoding (IAPE) proviral elements in the mouse genome encode and express an envelope-like protein that may allow transmission of IAPEs as infectious agents. To test IAPE mobility and potential transmission in mice, we have analyzed the distribution of IAPE elements in the genomes of Mus spretus and Mus musculus inbred strains and wild-caught animals. Potential full-length (IAPE-A) proviral elements are present as repetitive copies in DNA from male but not female animals of M. musculus inbred strains and Mus musculus castaneus. Analysis of IAPE-cellular junction fragments indicates that fixation of most IAPEs in the germ line occurred in M. musculus and M. spretus after speciation but before M. musculus inbred strains were derived.     

Morphological demonstration of the failure of Mus caroli trophoblast in the Mus musculus uterus

A histological study of Mus caroli embryos gestating in the Mus musculus uterus was undertaken at Day 8.5 of gestation, 1 day after such embryos are reported to be normal and 1 day before the earliest events associated with death of the xenogeneic embryos. In comparison to control M. caroli embryos recovered from M. caroli and to control M. musculus embryos recovered from M. musculus, the xenogeneically transferred embryos showed intrauterine growth retardation that was associated with trophoblastic insufficiency. Trophoblast cell degeneration was observed, in the absence of lymphocytic infiltration. Therefore, loss of trophoblast cell function rather than lymphocyte-mediated destruction of trophoblast appears to underlie the death of M. caroli embryos in the M. musculus uterus.     

PCR-analyzed microsatellites: Data concerning laboratory and wild-derived mouse inbred strains

We have investigated 67 primers designed by Dr. J. Todd and co-workers to amplify microsatellites sequences in the mouse. We report on additional polymorphisms concerning seven laboratory inbred strains, complementary to those already published. We include the survey of three independently derived strains of Mus spretus: SPE/Pas, SEG/Pas and SPR/Smh. SPE/Pas and SEG/Pas are very close (3% polymorphism), whereas the third one, (SPR/Smh), is very different from the other two strains (33% polymorphism). Seventy-four to 84% of the microsatellites analyzed in this study are polymorphic between C57BL/6Pas and Mus spretus strains. By comparison, 36–46% are polymorphic between laboratory inbred strains involved in established sets of recombinant inbred strains. A strain derived from Mus musculus musculus (PWK/Pas) was found to be very different from both C57BL/6Pas (70% polymorphism) and SPE/Pas (82% polymorphism). These results emphasize the interest of using Mus musculus musculus inbred strains to establish interspecific crosses, particularly when considering their breeding performances.     

Susceptibility of natural hybrids between house mouse subspecies to Sarcocystis muris

A previous study showed that the susceptibility of hybrids between two Mus musculus musculus and Mus musculus domesticus did not apply to every parasite. The authors proposed that only parasites which exerted enough constraints would induce the selection of poorly compatible systems of resistance in the subspecies. This study completes the previous work. Experimental infections of mice of the two subspecies and their hybrids with the tissue-dwelling protozoan Sarcocystis muris show that hybrids are more susceptible to the coccidian than M. m. musculus and M. m. domesticus individuals. This result demonstrates that the hybrids are not only susceptible to intestinal helminths, and confirms the 'constraint hypothesis'.     

Risk of accidental invasion and expansion of allochthonous mice in Tokyo metropolitan coastal areas in Japan

House mouse (Mus musculus) is one of the perilous animal vectors for imported zoonosis such as a lymphocytic choriomeningitis (LCMV) infectious disease, and probably unknown emerging and/or re-emerging infectious diseases as well. It is necessary to prevent such diseases by regular surveys for behavioral trends of these allochthonous mice. However, such a trial has never been attempted in Japan. From 1998 to 2002, we analyzed partial sequences of the D-loop region in mtDNA, which provides powerful diagnostic SNPs for subspecies identification in the Mus musculus species, from 301 individuals of mice collected in 23 international bays or airports in Japan. We found that invasion of many allochthonous mice, which were identified as European subspecies, Mus musculus domesticus, occurred in Tokyo metropolitan coastal area. Based on the evidence, we warn that extensive invasion of allochthonous mice has occurred recently and, therefore, the risk of emerging and/or re-emerging infectious diseases invasion might be high in Tokyo metropolitan area.     

Satellite DNA as a phylogenetic marker: Case study of three genera of the murine subfamily

Satellite DNA (satDNA) represent tens of percent of the vertebrate genome. However, no full set of satDNA fragments has been determined for even one species. It is known that some genera possess a satDNA characteristic for that genus with species-specific modifications. We found that the pattern of hybridization of Mus musculus satDNA probes with M. spicilegus metaphase chromosomes was similar to, with slight differences from, that of M. musculus. No hybridization signal was observed if Mus musculus satDNA probes were hybridized with representatives of Sylvaemus and Apodemus genera. The amount of Mus musculus satDNA in the genomes of various species was evaluated by dot-hybridization. We revealed that genomes of close murine species had cenromeric and pericentromeric repeats belonging to the same families and were not found in remote species.     

Molecular evolution of a Y-chromosomal repetitive sequence family in the genus Mus

A 522-base-long Y-chromosomal sequence was isolated from a BALB/c genomic library and was designated "BF046." It is repeated about 200 times in the male genome, and a difference was detected between the Mus musculus musculus and the M. m. domesticus type Y chromosomes. BF046- related sequences were present over the entire length of the Y chromosome as visualized by in situ hybridization. Southern blot analysis against DNAs isolated from eight species in the genus Mus showed that BF046-related sequences were amplified in the Y chromosomes of three closely related species: M. musculus, M. spicilegus, and M. spretus. To gain insight into the stability of the BF046 sequence family, we isolated 18 additional clones from these three mouse species and compared their sequences. The M. musculus sequences differed from the M. spicilegus and M. spretus sequences by two indels. The remaining parts of the sequences were very similar, but both parsimony and distance-based analytical methods divided the sequences into the same four subgroups, with each species having its own subgroup(s). Thus, the Y chromosomes of M. musculus, M. spicilegus, and M. spretus can be distinguished from one another.