Amplified ribosomal spacer sequence: structure and evolutionary origin

A novel class of repeated sequences consisting of tandem arrays of ribosomal spacer sequence has been discovered in a mouse genome. Comparison to normal ribosomal DNA reveals that one repeat unit consists of two separate parts of spacer sequence. This amplified spacer sequence has a pseudogene-like structure but is distinct from the previously reported pseudogenes and orphons in regions lacking coding sequences. So far the amplified spacer sequence has been found only in the BALB/c mouse genome but not in ten other laboratory strains and several wild-type mouse stocks. Surprisingly, a part of the amplified spacer sequence unit had a higher homology to the corresponding part of the ribosomal DNA sequence of Mus musculus molossinus, a Japanese wild-type mouse, than to the corresponding part of the rDNA of the BALB/c mouse. These findings suggest that the amplified spacer sequence of the BALB/c mouse might have partly originated in M. m. molossinus or in a related subspecies.     

Modes of inheritance of X-Y dissociation in inter-subspecies hybrids between BALB/c mice and Mus musculus molossinus

Genetic analysis of the high frequency of X-Y chromosome dissociation found in primary spermatocytes of F1 hybrids between Japanese wild mice (Mus musculus molossinus) and inbred laboratory mice (BALB/c) was attempted. The frequency of X-Y dissociation (X//Y) in both BALB/c and M. m. molossinus was lower than 30% (Low X//Y), while the value was more than 70% (High X//Y) in their F1 hybrids. Two types of progeny (High X//Y and Low X//Y) appeared in the backcross between BALB/c and High X//Y males, although the frequency of Low X//Y progeny decreased with increasing numbers of backcross generations (26.5% at N2, 13.2% at N3, 5.3% at N4, and 0% at N5). Low X//Y sires produced only Low X//Y mice. We hypothesize that at least one heritable factor which is responsible for the end-to-end association of the sex chromosomes (temporally symbolized as Sxa) is located on the common part of the X and Y chromosomes. The Sxa allele of BALB/c is Sxaa and that of M. m. molossinus is Sxab. The genotype expected in High X//Y males is Sxaa/Sxab and in Low X//Y males and their parental stocks either Sxaa/Sxaa or Sxab/Sxab. The repeated segregation of Low X//Y progeny from High X//Y sires is interpreted simply by assuming that crossing-over has occurred between the X and Y chromosomes. The gradual decrease in the recombinant type mice (Low X//Y) during sequential backcrosses suggests the presence of some autosomal factors that suppress the crossing-over of the sex chromosomes and that do not seem to function in the inter-subspecies hybrids.     

Variation in the distribution of silver-staining nucleolar organizer regions on the chromosomes of the wild mouse, Mus musculus.

A silver staining method was used to analyze the distribution of nucleolar organizer regions (Ag-NORs) on chromosomes of 45 wild mice (Mus musculus). The four subspecies represented were M. m. musculus, M. m. molossinus, M. m. castaneus, and M. m. bactrianus. Ag-NORs were observed near the centromeric regions of 11 chromosomes (4, 8, 9, 10, 11, 12, 15, 16, 17, 18, and 19), indicating a preponderance of Ag-NORs on smaller chromosomes. The first five loci have not been observed previously. It is suggested that a correlation may exist between the specific features of mouse Ag-NORs and the events involved in intra- and interchromosomal homogenization of rDNA.     

Physical performance and soleus muscle fiber composition in wild-derived and laboratory inbred mouse strains.

We compared four inbred mouse strains in their physical performance, measured as a maximal treadmill running time, characteristics of soleus muscle, anatomic character, and growth. The strains used were Mus musculus domesticus [C57BL/6 (B6) and BALB/c], Mus musculus molossinus (MSM/Ms), and Mus spretus. Maximal running time was significantly different among these four mouse strains. Running time until exhaustion was highest in MSM/Ms and lowest in M. spretus. Maximal times for the laboratory mouse strains were nearly identical. Soleus muscle fiber type and cross-sectional area also differed significantly among the species. In particular, M. spretus was significantly different from the other inbred mouse strains. Growth in the wild-derived inbred mice appeared to be complete earlier than in the laboratory mice, and the body size of the wild strains was about half that of the laboratory strains. From these results, we propose that wild-derived inbred mouse strains are useful models for enhancing phenotypic variation in physical performance and adaptability.     

Differing populations of intracisternal A-particle genes in myeloma tumors and mouse subspecies.

Intracisternal A-particle genes form a family of endogenous retrovirus-like genetic elements that are transcribed in mouse plasmacytomas (myeloma tumors). Two types of A-particle genes that can be differentiated by a sequence of 0.5 kilobase found in one type but not the other have been identified. Quantitative Southern blot analysis was used to measure the populations of different A-particle genes in DNAs from BALB/c mice, the Japanese subspecies Mus musculus subsp. molossinus, and myeloma tumors. The majority of the genes (715 copies per haploid genome or 76%) were found to be nearly identical except for small changes in conserved restriction enzyme sites. The second type of A-particle gene was much less abundant with 90 copies representing approximately 10%. The A-particle RNA in MOPC104E and MOPC315 was found to be colinear with a small portion of this latter type, comprising only 2% of the endogenous intracisternal A-particle sequences. Myeloma tumor DNA was found to have a two- to fourfold increase in the number of these genes, suggesting that the intracellular viruses have been activated to produce a double-stranded complementary DNA which subsequently integrated into the tumor genome. Analysis of M. musculus subsp. molossinus DNA revealed similar but shifted populations of A-particle genes, when compared with BALB/c DNA, except for the absence of a prominent EcoRI-HindIII band at 3.9 kilobases. This latter band, representing approximately 15% of the A-particle genes in BALB/c DNA, was shown to be a deletion variant of the most abundant gene family.     

Nucleotide sequence of endothelin-B receptor gene reveals origin of piebald mutation in laboratory mouse.

Piebald (Ednrbs) is a coat color mutation of laboratory mice caused by a decreased expression of endothelin-B receptor gene (Ednrb). The IITES and JF1 mouse strains, whose origins are believed to be different from those of the common laboratory inbred strains, also show a phenotype similar to Ednrbs. In the present study, we found that the nucleotide sequence of the Ednrb gene of the IITES and JF1 mice is identical to that of the Ednrbs allele, Ednrbs allele has an RFLP of the Ednrb gene identical with that of M. m. molossinus but different from other subspecies, and at least particular regions of chromosome 14 proximal to the Ednrb locus of the IITES and JF1 strains are derived from M. m. molossinus. These findings clearly indicate that the Ednrbs allele of the laboratory mice has its origin in M. m. molossinus.     

Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice

When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is replaced by the Y of certain strains of Mus musculus domesticus, testis determination fails and all XY fetuses develop either as hermaphrodites or XY females (XY sex reversal). This suggests the presence of at least two alleles of Sry, the male-determining gene on the Y:M. m. domesticus and B6. The B6 Y chromosome is derived from the Japanese house mouse, M. m. molossinus and therefore carries a molossinus Sry allele. As a first step to determine how the molossinus Sry allele evolved, its distribution pattern was determined in wild mice. The cumulative data of 96 M. musculus samples obtained from 58 geographical locations in Europe, North Africa, and Asia show the molossinus Sry allele is restricted to Japan and the neighboring Asian mainland and confirm that Japanese M. m. molossinus mice were derived in part from a race of M. m. musculus from Korea or Manchuria. Sry polymorphisms, as illustrated by the molossinus Sry allele, can serve as molecular markers for studies on the evolution of wild M. musculus populations and can help determine the role sex determination plays in speciation.      

Origins of Laboratory Mice Deduced from Restriction Patterns of Mitochondrial DNA

To determine the origins of laboratory mice, the restriction patterns of mitochondrial DNAs (mtDNAs) from various strains were compared with those of relevant subspecies and/or races of mus musculus . In most strains and substrains of laboratory mice examined (50/55), the cleavage patterns were identical to those of the European subspecies M. m. domesticus . Those that varied include two sublines of NZB, the strain NZC, and the Japanese strain RR. The NZB and NZC patterns were identical to that of the European subspecies M. m. brevirostris , which itself has restriction patterns similar to M. m. domesticus . On the other hand, the RR pattern was identical to M. m. molossinus -like mice trapped in Western China and slightly different from Japanese M. m. molossinus . These findings suggest that the strains NZB and NZC stemmed from a European founder stock which differed from the ancestral stocks of other laboratory strains and that the ancestral mice of the RR strain had been transported from China to Japan. Therefore, most laboratory strains of mice are derived from the European subspecies M. m. domesticus while M. m. brevirostris and M. m. molossinus have made minor contributions. M. m. musculus does not appear to have made any contribution.     

Acquisition of two endogenous ecotropic murine leukemia viruses in distinct Asian wild mouse populations.

Wild mouse DNAs were analyzed for two types of endogenous ecotropic murine leukemia viruses (MuLVs), Akv and Fv-4r-associated MuLV. Endogenous Akv viruses were found only in northern Chinese mice, Korean mice, and Japanese (Mus musculus molossinus) mice. The Fv-4r gene, which is a truncated endogenous MuLV with ecotropic interference properties, was carried by Southeast Asian (M. m. castaneus) mice, Korean mice, and M. m. molossinus. Sequences related to Fv-4r MuLV env were found only in M. m. castaneus. These findings suggest that endogenous Akv viruses were acquired by northern Chinese mice and that the Fv-4r gene or its related endogenous MuLVs were acquired independently by M. m. castaneus. The Fv-4r gene appears to have been generated hundreds of thousands of years ago, before the amplification of the Fv-4r-related endogenous MuLVs in M. m. castaneus. The coexistence of Akv viruses and the Fv-4r gene in M. m. molossinus may be explained by the hybrid origin of M. m. molossinus in crosses between northern Chinese mice and M. m. castaneus, as described in other articles. The absence of the Fv-4r-related endogenous MuLVs in M. m. molossinus may indicate that the ancestral mice of this subspecies either were an ancient type of M. m. castaneus that had acquired the Fv-4r gene but had not yet acquired the Fv-4r-related endogenous MuLVs or were a rare fraction of a mixed population of M. m. castaneus and northern Chinese mice.     

Establishment of a congenic strain with complement regulatory protein of factor H allotype derived from Mus. musculus molossinus]

Factor H is a plasma glycoprotein with M. W of 160 KDa which serves as one of the regulatory proteins for C 3 convertases. We have previously reported three serologically defined mouse factor H allotypes by surveying many laboratory and wild mice. In the present work, we established a congenic strain with factor H allotype, H. 2. on BALB/c (H. 1 allotype) background and named this strain BALB-H.2. Alloantiserum against each allotype has been easily prepared using two congenic strains by immunization with a small amount of whole mouse serum. BALB-H.2 is valuable for the genetic studies on the genes in the vicinity of factor H gene (cfh) derived from Mus. m. molossinus.     

Hybrid origin of Japanese mice "Mus musculus molossinus": evidence from restriction analysis of mitochondrial DNA

The Japanese mouse, Mus musculus molossinus, has long been considered an independent subspecies of the house mouse. A survey of restriction- site haplotypes of mitochondrial DNA (mtDNA) showed that Japanese mice have two main maternal lineages. The most common haplotype is closely related to the mtDNA of the European subspecies M. m. musculus. The other common haplotype and two minor ones are closely related to each other and to the mtDNA of an Asiatic subspecies, M. m. castaneus. Two other rare variants are probably the result of recent contamination by European M. m. domesticus. The musculus type of mtDNA is found in the southern two-thirds of Japan, whereas the common castaneus type is found in the northern third and the minor variants are found sporadically throughout Japan. The castaneus mtDNA lineage had a few minor variants, whereas the musculus lineage was completely monomorphic. By contrast, the native population of M. m. castaneus and the Chinese and Korean musculus populations were highly polymorphic. These results suggest that M. m. molossinus is a hybrid between ancestral colonies, possibly very small, of M. m. musculus and M. m. castaneus, rather than an independent subspecies.      

Origins of laboratory mice deduced from restriction patterns of mitochondrial DNA

To determine the origins of laboratory mice, the restriction patterns of mitochondrial DNAs (mtDNAs) from various strains were compared with those of relevant subspecies and/or races of Mus musculus. In most strains and substrains of laboratory mice examined (50/55), the cleavage patterns were identical to those of the European subspecies M. m. domesticus. Those that varied include two sublines of NZB, the strain NZC, and the Japanese strain RR. The NZB and NZC patterns were identical to that of the European subspecies M. m. brevirostris, which itself has restriction patterns similar to M. m. domesticus. On the other hand, the RR pattern was identical to M. m. molossinus-like mice trapped in Western China and slightly different from Japanese M. m. molossinus. These findings suggest that the strains NZB and NZC stemmed from a European founder stock which differed from the ancestral stocks of other laboratory strains and that the ancestral mice of the RR strain had been transported from China to Japan. Therefore, most laboratory strains of mice are derived from the European subspecies M. m. domesticus while M. m. brevirostris and M. m. molossinus have made minor contributions. M. m. musculus does not appear to have made any contribution.     

Laboratory and wild-derived mice with multiple loci for production of xenotropic murine leukemia virus.

Mendelian segregation analysis was used to define genetic loci for the induction of infectious xenotropic murine leukemia virus in several laboratory and wild-derived mice. MA/My mice contain two loci for xenotropic virus inducibility, one of which, Bxv -1, is the only induction locus carried by five other inbred strains. The second, novel MA/My locus, designated Mxv -1, is unlinked to Bxv -1 and shows a lower efficiency of virus induction. The NZB mouse carries two induction loci; both are distinct from Bxv -1 since neither is linked to the Pep-3 locus on chromosome 1. Finally, one partially inbred strain derived from the wild Japanese mouse, Mus musculus molossinus, carries multiple (at least three) unlinked loci for induction of xenotropic virus. Although it is probable that inbred strains inherited xenotropic virus inducibility from Japanese mice, our data suggest that none of the induction loci carried by this particular M. m. molossinus strain are allelic with Bxv -1.     

Reduced expression of STAT4 and IFN-gamma in macrophages from BALB/c mice

BALB/c mice have been shown to easily induce Th2 type responses in several infection models. In this study, to examine the mechanisms of Th2 dominant responses in BALB/c mice, we assessed several macrophage functions using C3H/HeN, C57BL/6, and BALB/c mouse strains. Peritoneal macrophages from three strains of mice equally produced IL-12 by stimulation with LPS plus IFN-gamma. However, IFN-gamma production in response to IL-12 or IL-12 plus IL-18 was much lower in macrophages from BALB/c mice than other strains. IFN-gamma produced by activated macrophages induced IL-12R mRNA expression in T cells and macrophages themselves depending on their amount of IFN-gamma; namely, macrophages from BALB/c mice induced lower expression of IL-12R. Intracellular levels of STAT4 were much lower in macrophages from BALB/c mice. However, other STATs, such as STAT1 or STAT6, were expressed similarly in the three mouse strains. STAT4 and IFN-gamma production by other cell types such as T cells and B cells were equal in C3H/HeN and BALB/c mice. These results indicate that macrophages from Th2-dominant BALB/c mice have different functional characters compared with other mouse strains; that is, STAT4 expression and IFN-gamma production are reduced, which is one of the causes to shift to Th2-type responses.     

Phylogeographic origin of Hokkaido house mice (Mus musculus) as indicated by genetic markers with maternal, paternal and biparental inheritance

We examined intraspecies genetic variation in house mice (Mus musculus molossinus) from the northern third of the Japanese Islands, in order to obtain evidence of the history of mouse colonization that might have shaped the current genetic diversity. We extended the previous sampling of mitochondrial cytochrome b sequence and added information from the Y-linked Sry gene and ribosomal RNA gene surveys. We distinguish mitochondrial haplotypes characteristic of the North Asian musculus subspecies group (involving M. m. musculus and M. m. molossinus) as 'MUS', and that of the Southeast Asian castaneus subspecies group as 'CAS' (although the mice resemble MUS morphologically). There was a clear geographic partition of MUS and CAS types into southern and northern Hokkaido, respectively. Conversely, on Tohoku, the MUS and CAS types were interspersed without clear geographic subdivision. In contrast to the mtDNA data, all Hokkaido and Tohoku mice examined were found to possess a unique type for the Y-linked Sry gene, specific to Korea and Japan. Restriction site analysis of nuclear rDNA probe showed a consistent distribution of MUS and CAS types, as major and minor components, respectively, in the Hokkaido and Tohoku mice. These data support the previous notion that the Hokkaido and Tohoku mice experienced genetic hybridization between primary residents of CAS origin and MUS newcomers arriving via a southern route. The invasion of the MUS type could correspond with the evidence for arrival of prehistoric peoples. There are, however, alternative interpretations, including genetic admixture between MUS arriving by a southern route and CAS from a northern route.     

Locations of three repetitive sequence families found in BALB/c adult beta-globin clones.

Three different repeat sequences have been mapped within the cloned EcoRI fragments that contain the adult beta-globin genes from the BALB/c (Hddd) mouse. One sequence, "a", occurs 1.5-2 kb 3' to the beta-major gene. A second, "b", is found 4kb 5' and 7.5kb 3' to the beta-minor gene. The 14kb EcoRI fragment bearing the beta-minor gene carries at least one additional repetitive element, "c". Probing a BALB/c DNA library with each repeat has demonstrated that these sequences are moderately to highly repetitive and are extensively interspersed with each other throughout the genome. In addition, repeats "a" and "b" are preferentially found in satellite and main-band DNa, respectively. The occurrence of these repeats elsewhere in the beta-globin cluster was demonstrated by probing the non-adult globin clones with each repeat. The arrangement of these repeats around the non-adult genes is 5'-"b"-"b"-epsilon y-beta hl-beta h2-"c"-beta h3-3'. Probing the C57BL/10 (Hbbs) adult gene clones with these repeats demonstrated that the distribution of these sequences in the adult region of these two haplotypes is essentially the same.     

Isolation and characterization of the highly repeated fraction of the banana genome

Although the nuclear genome of banana (Musa spp.) is relatively small (1C approximately 610 Mbp for M. acuminata), the results obtained from other sequenced genomes suggest that more than half of the banana genome may be composed of repetitive and non-coding DNA sequences. Knowledge of repetitive DNA can facilitate mapping of important traits, phylogenetic studies, BAC-based physical mapping, and genome sequencing/annotation. However, only a few repetitive DNA sequences have been characterized in banana. In this work, we used DNA reassociation kinetics to isolate the highly repeated fraction of the banana genome (M. acuminata 'Calcutta 4'). Two libraries, one prepared from Cot 相似文献   

Mouse IgA allotypes have major differences in their hinge regions

Six IgA allotypes are serologically identifiable in inbred mice. The sequences of the PCR-amplified C alpha 1, C alpha 2 and C alpha 3 exons from the genomic DNA of mice of four previously unsequenced allotypes already have been compared with those of BALB/c and of a wild mouse, Mus pahari, in the literature. Sporadic differences, including several that may encode the known allotypic determinants, are found throughout the three exons, but major differences occur in the hinge. The hinge is longest in DBA/2 ( Igh-2(c)) mice, having an extra codon compared with that of BALB/c ( Igh-2(a)) and B10.A ( Igh-2(b)) mice. It is two codons shorter in CE ( Igh-2(f)) and four shorter in M. pahari, AKR and NZB (both Igh-2(d)) mice, but the position of the missing codons in the latter two strains is offset from that in M. pahari. The hinges in BALB/c ( Igh-2(a)) and DBA/2 ( Igh-2(c)) differ most from each other and from the other three allotypes, which are fairly closely related. Both BALB/c and DBA/2 have O-linked glycosylation sites, but they are in different positions in the hinge. Compared with BALB/c ( Igh-2(a)), B10.A( Igh-2(b)) has two extra Cys residues in the hinge, while DBA/2 ( Igh-2(c)), AKR/NZB ( Igh-2(d)) and CE ( Igh-2(f)) each have one. The differences in hinge length may have arisen by mismatching of highly repetitive portions of its sequence during meiotic recombination. Possible effects of the differences in hinge length and composition on the behavior of the mouse IgA allotypes are discussed.