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T Shiroishi

Publications and source records attributed to T Shiroishi.

At least 73 records · Page 4Linked to original sources
PubMed1994

Recombination in the class III region of the mouse major histocompatibility complex.

The sites of meiotic recombination in the class II region of the mouse major histocompatibility complex (MHC) are clustered at hotspots. To search for hotspots in the class III region, we mapped recombinational breakpoints of 79 Ab:H2-D recombinants with 11 DNA markers; these included Tnx, the gene for an extracellular matrix protein, tenascin X, the Notch-related Int3 gene, and a microsatellite marker, D17Mit13, none of which had previously been mapped precisely. The results gave the gene order of Eb-61.1-Int3-Tnx-Cyp21/C4-Bf-Hsp68c-D17Mit13+ ++-Tnfa/Tnfb-D. The crossover sites in 40 of the 79 recombinants were confined within the Eb/Int3:Tnx/Cyp21 interval. The result demonstrated that an unequal distribution of recombination is a general feature of the mouse MHC, suggesting the presence of a recombinational hotspot within the Int3:Tnx interval.

Animals↗
PubMed1994

Novel mouse microsatellites: primer sequences and chromosomal location.

Sixty-nine sequences containing microsatellites were determined by analysis of clones from a pUC118 library of total genomic mouse DNA. These sequences were examined for size variation using polymerase chain reaction and gel electrophoresis. Fifty-one of them showed allelic variations between C57BL/6 and MSM, the two strains used for genetic mapping. Hence, their chromosomal location was determined using a panel consisting of 131 backcross mice that had been typed with 85 anchor loci. The microsatellites were distributed to most chromosomes except for chromosomes 16 and 19. These novel markers with defined locations are useful in linkage and genome mapping studies.

Animals↗
PubMed1994

A genetic linkage map of the mouse using restriction landmark genomic scanning (RLGS).

We have developed a multiplex method of genome analysis, restriction landmark genomic scanning (RLGS) that has been used to construct genetic maps in mice. Restriction landmarks are end-labeled restriction fragments of genomic DNA that are separated by using high resolution, two-dimensional gel electrophoresis identifying as many as two thousand landmark loci in a single gel. Variation for several hundred of these loci has been identified between laboratory strains and between these strains and Mus spretus. The segregation of more than 1100 RLGS loci has been analyzed in recombinant inbred (RI) strains and in two separate interspecific genetic crosses. Genetic maps have been derived that link 1045 RLGS loci to reference loci on all of the autosomes and the X chromosome of the mouse genome. The RLGS method can be applied to genome analysis in many different organisms to identify genomic loci because it uses end-labeling of restriction landmarks rather than probe hybridization. Different combinations of restriction enzymes yield different sets of RLGS loci providing expanded power for genetic mapping.

Animals↗
PubMed1994

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.

Alleles↗
PubMed1994

Survival of steroid 21-hydroxylase-deficient mice without endogenous corticosteroids after neonatal treatment and genetic rescue by transgenesis as a model system for treatment of congenital adrenal hyperplasia in humans.

The genome of mice with the H-2aw18 haplotype has a deletion of approximately 80 kilobases in the H-2 class III region of chromosome 17. Mice that are homozygous for the mutation die soon after birth. A functional form of steroid 21-hydroxylase (21-OHase) is encoded by the deleted DNA fragment, and H-2aw18 homozygotes are deficient in this enzyme. 21-OHase catalyzes the conversion of progesterone to deoxycorticosterone during adrenal steroidogenesis in mice; therefore, H-2aw18 homozygous mice are unable to synthesize corticosteroids. The deleted region also includes the gene for complement component C4, which has a role in the classical pathway of the complement activation cascade. To clarify the cause of the lethality of the mutation, we first administered either an adrenal homogenate or synthetic steroids to newborn mice; as a result, several H-2aw18 homozygotes were rescued. The results demonstrated that the mutant mice die as the result of a defect in adrenal steroidogenesis. The low efficiency of the rescue by treatment of newborns (16.0% by the adrenal homogenate and 14.8% by the synthetic steroids) suggested that mutant mice should be treated prenatally. Moreover, because the 21-OHase gene is expressed before birth, introduction of a gene for 21-OHase should improve the efficiency of rescue. The results of the murine mutation are similar to those of the inherited human disease known as congenital adrenal hyperplasia, which is caused by steroid 21-hydroxylase deficiency. As a model system for treatment of the human disease by genetic therapy, we used transgenic approaches to introduce a recombinant DNA fragment containing the murine genomic gene for 21-OHase into the mutant mice. We produced four lines of transgenic mice, and in all four transgenic lines, the transgene rescued the lethal mutation. The apparent efficiencies of rescue were 80.2%, 80.0%, 68.7%, and 16.7% for the respective lines of transgenic mice. During the course of our experiments, we also found an unexpected property associated with the role of corticosteroids. The H-2aw18 homozygous mice rescued by neonatal treatment survived for a long period without further treatment. This observation indicates that corticosteroids down-stream of 21-OHase in the pathway for adrenal steroidogenesis are not essential for the survival of mice, except during the period immediately after birth.

Adrenal Cortex Hormones↗
PubMed1993

Molecular cloning of the b subunit of mouse coagulation factor XIII and assignment of the gene to chromosome 1: close evolutionary relationship to complement factor H.

The b subunit of human coagulation factor XIII (FXIII-b) is composed of 10 short consensus repeats (SCRs) characteristic of the regulatory proteins of complement activation system. A full-length cDNA clone of mouse FXIII-b was isolated and the entire sequence was determined. The predicted amino acid sequence showed 77.5% homology with human FXIII-b, although mouse FXIII-b contained seven extra amino acid residues at the carboxyl terminal. The strong reactivity of the translation product of this clone with rabbit anti-human FXIII-b antiserum confirmed that it encodes a mouse counterpart of the human FXIII-b. By in situ hybridization and mapping studies using 66 interspecific backcross mice, the mouse FXIII-b gene (designated F13b) was shown to be located on distal chromosome 1 closely linked to Cfh, extending a conserved linkage group between human and mouse chromosome 1. In addition, a significant structural similarity between FXIII-b and complement factor H is described.

Amino Acid Sequence↗
PubMed1993

Hotspots of meiotic recombination in the mouse major histocompatibility complex.

Meiotic recombination is not random in the proximal region of the mouse major histocompatibility complex (MHC). It is clustered at four restricted positions, so-called hotspots. Some of the MHC haplotypes derived from Asian wild mice enhance recombination at the hotspots in genetic crosses with standard MHC haplotypes of laboratory mouse strains. In particular, the wm7 haplotype derived from Japanese wild mouse indicated an approximately 2% recombination frequency within a 1.2 kb fragment of DNA in the interval between the Pb and Ob genes. Interestingly, this enhancement of recombination was observed only in female meiosis but not in male meiosis. Mating experiments demonstrated that the wm7 haplotype carries a genetic factor in the region proximal to the hotspot, which instigates recombination. In addition, the wm7 haplotype has a genetic factor located in the region distal to the hotspot, which suppresses recombination. From the molecular characterization of the two hotspots located in the Eb gene and the Pb-Ob interval, it appeared that there are several common molecular elements, the consensus of the middle repetitive MT-family, TCTG or CCTG tetramer repeats, and the solitary long terminal repeat (LTR) of mouse retrovirus.

Animals↗
PubMed1992

Molecular cloning of mouse beta 2-glycoprotein I and mapping of the gene to chromosome 11.

beta 2-Glycoprotein I (beta 2 GPI), a plasma protein that binds to anionic phospholipids, is composed of five repeating units called a short consensus repeat (SCR), which is found mostly in the regulatory proteins of the complement system. Recently the human beta 2 GPI gene has been assigned to chromosome 17, not to chromosome 1 where most of the genes of the SCR-containing proteins are clustered. In this report, we have isolated a full-length cDNA clone of mouse beta 2 GPI and determined the chromosomal localization of the gene. The amino acid sequence deduced from the nucleotide sequence of mouse beta 2 GPI revealed 76.1% identity with that of human beta 2 GPI. A genetic mapping by in situ hybridization and linkage analysis using 50 backcross mice has shown that the mouse beta 2 GPI gene (designated B2gp1) is located on the terminal portion of the D region of chromosome 11, closely linked to Gfap, and is 18 cM distal to Acrb, extending a conserved linkage group between mouse chromosome 11 and human chromosome 17. On the basis of these results, the evolutionary relationships among the SCR-containing proteins are discussed.

Amino Acid Sequence↗
PubMed1992

The amplified long genomic sequence (ALGS) located in the centromeric regions of mouse chromosomes.

We reported previously that the haploid genome of standard strains of laboratory mice contains approximately 70 copies of an amplified long genomic sequence, designated ALGS, that includes a retroposon of the gene for elongation factor 2 (MER). The length of each repeating unit is more than 60 kb, and the sequence of the unit is highly conserved among the repeats. In the present study, Southern blot analysis of the genomes of wild rodents demonstrated that the ALGS is present in all subspecies of Mus musculus and is abundant in M. spicilegus, whereas it is absent in M. spretus as well as in Rattus and other closely related genera. This result indicates that the amplification occurred after the species differentiation with the genus Mus and at least prior to the differentiation of subspecies of M. musculus. To locate chromosomal positions of the ALGS, in situ hybridization was carried out with laboratory strains and wild mice. It appears that the ALGS is located in the centromeric regions of most chromosomes in laboratory mice, M. musculus and M. spicilegus, whereas no positive signals were observed with M. spretus, in accordance with the results from the Southern blotting analysis.

Animals↗
PubMed1991

Molecular cloning and structural analysis of mouse gene and pseudogenes for proliferating cell nuclear antigen.

We have isolated clones containing the entire mouse proliferating cell nuclear antigen (PCNA) gene of 3890 bp and flanking sequences using a rat PCNA cDNA as a probe. The mouse gene has 6 exons whose sequences and junction points of exons with introns are extensively homologous to the human gene while sizes and nucleotide sequences of introns are much less conserved than exons. By a transient expression assay of chloramphenicol acetyltransferase, the promoter of this gene is localized within 200 bp upstream of the transcription initiation site. We have also isolated two processed pseudogenes. Homology between the first one (psi PCNA-I) and the exons of the PCNA gene was 76.8% in the region so far sequenced. The second one (psi PCNA-II) consists of a region highly homologous to the entire exons of the PCNA gene, and only 9 out of total 1256 bp are different from the corresponding exon sequence of the gene. The 5'-flanking region of the psi PCNA-II did not function as an active promoter. Surveys in various wild and laboratory mice genomes suggest that the psi PCNA-II was generated through the reverse transcription process of the PCNA mRNA about 5 x 10(5) years ago in the domesticus subspecies of Mus musculus, the house mouse. The psi PCNA-II is tentatively mapped in the chromosome 17 of the C57BL mouse.

Amino Acid Sequence↗
PubMed1991

Genetic control of sex-dependent meiotic recombination in the major histocompatibility complex of the mouse.

Meiotic recombination within the proximal region of the major histocompatibility complex (MHC) of the mouse is not random but occurs in clusters at certain restricted sites, so-called recombinational hotspots. The wm7 haplotype of the MHC, derived from the wild mouse, enhances recombination specifically during female meiosis within a fragment of 1.3 kb of DNA located between the A beta 3 and A beta 2 genes in genetic crosses with laboratory haplotypes. Previous studies revealed no significant strain differences in nucleotide sequences around the hotspot, irrespective of the ability of the strain to enhance the recombination. It appeared that a distant genetic element might, therefore, control the rate of recombination. In the present study, original recombinants whose breakpoints were defined by direct sequencing of PCR-amplified DNAs were tested for the rate of secondary recombination in the crosses with laboratory strains in order to determine the location of such a genetic element. The results clearly demonstrated that the chromosomal segment proximal to the hotspot is essential for enhancement of recombination. Moreover, the male recombination is suppressed by a segment distal to the hotspot.

Alleles↗
PubMed1990

Recombinational hotspot specific to female meiosis in the mouse major histocompatibility complex.

The wm7 haplotype of the major histocompatibility complex (MHC), derived from the Japanese wild mouse Mus musculus molossinus, enhances recombination specific to female meiosis in the K/A beta interval of the MHC. We have mapped crossover points of fifteen independent recombinants from genetic crosses of the wm7 and laboratory haplotypes. Most of them were confined to a short segment of approximately 1 kilobase (kb) of DNA between the A beta 3 and A beta 2 genes, indicating the presence of a female-specific recombinational hotspot. Its location overlaps with a sex-independent hotspot previously identified in the Mus musculus castaneus CAS3 haplotype. We have cloned and sequenced DNA fragments surrounding the hotspot from the wm7 haplotype and the corresponding regions from the hotspot-negative B10.A and C57BL/10 strains. There is no significant difference between the sequences of these three strains, or between these and the published sequences of the CAS3 and C57BL/6 strains. However, a comparison of this A beta 3/A beta 2 hotspot with a previously characterized hotspot in the E beta gene revealed that they have a very similar molecular organization. Each hotspot consists of two elements, the consensus sequence of the mouse middle repetitive MT family and the tetrameric repeated sequences, which are separated by 1 kb of DNA.

Animals↗
PubMed1990

Amplification of a long sequence that includes a processed pseudogene for elongation factor 2 in the mouse.

Quantitative Southern blotting analysis has demonstrated that mouse cells contain about 70 copies per haploid genome of a DNA sequence related to the gene for elongation factor 2. The restriction maps of seven cosmids that each carry one copy of the EF2-related sequence (MER) and nucleotide sequences of MERs were highly conserved among the cosmids. Data obtained by such analyses suggest that MERs were produced by the integration of one copy of MER derived from poly(A)+ mRNA for EF2 into a specific site in the mouse genome, with subsequent amplification of MER together with its large flanking sequences during the evolution of the mouse. Furthermore, it appears that the size of each repeating unit is more than 60 kb. Analysis by pulse-field gel electrophoresis suggested that multiple copies of a repeating unit of more than 400 kb (or two units) are clustered at a specific site (or each specific site) in the mouse genome.

Animals↗
PubMed1989

Polymorphism of T-cell receptor genes among laboratory and wild mice: diverse origins of laboratory mice.

Southern blots of genomic DNA from 23 strains of laboratory mice and 19 individual wild mice were examined for restriction fragment length polymorphisms in their loci encoding the T-cell receptors (Tcr): the constant regions of the alpha, beta, and gamma chains (C alpha, C beta, and C gamma) and a variable region family of the beta chain (V beta 8). Only a few polymorphisms were observed for each locus in the laboratory mice after using three restriction enzymes, Bam HI, Eco RI, and Hind III. All the laboratory mice examined fall into one of two types for the C alpha, C beta, and V beta 8 loci and one of three types for the C gamma. These types are found in some of the wild mice studied, indicating that they were already present in the founder mice of laboratory mouse strains. In contrast, the Tcr genes are highly polymorphic among wild mice. Analysis of the polymorphisms in these loci suggests that laboratory mice have inherited their genes not only from Mus musculus domesticus, but also from other subspecies, and much more than previously believed from Asian subspecies.

Animals↗
PubMed1989

New evidence for trans-species evolution of the H-2 class I polymorphism.

A serological survey using alloantisera specific for the H-2 class I antigens in Japanese wild mice. Mus musculus molossinus, revealed a high frequency of the H-2Kf antigen. This antigen has also been found in European wild mice, M. m. domesticus and M. m. musculus. In this survey, the H-2Kf antigen was characterized through the use of ten newly isolated monoclonal antibodies raised against cells of a Japanese wild mouse, and by Southern blot analysis using an H-2K locus-specific probe which hybridizes with the 3' end of the gene. The serologically identified H-2Kf antigens revealed several minor variations in reactivities to the monoclonal antibodies. However, all the antigens examined could be clearly separated into two types with respect to the restriction fragment length polymorphism (RFLP) pattern. The first type, found together with a single, characteristic RFLP pattern, was always associated with the presence of reactivity to one particular monoclonal antibody MS54. The second type, found to represent different RFLP patterns, is associated with the absence of reactivity to MS54. This concordance between the presence of an antigenic determinant and a particular RFLP was observed not only within Mus musculus subspecies but also in a different species: M. spretus, carrying the same antigenic determinant, gave an identical RFLP to that of the other MS54-positive Mus musculus subspecies. The data suggest that the antigenic determinant specific for MS54 is an ancient polymorphic structure which has survived the long period of diversification of Mus species (approximately 2-3 million years) without alteration, and is associated with a stable DNA structure at the 3' end of the H-2K gene.

Animals↗
PubMed1988

Steroid 21-hydroxylase deficiency in mice.

The enzyme steroid 21-hydroxylase (21-OHase) plays a key role in adrenal steroidogenesis. Defects in this enzyme are responsible for one of the most common inborn errors of metabolism in humans. Duplicated genes for the enzyme are located in the class III region of the major histocompatibility complex (MHC), HLA. In the mouse, the genes encoding 21-OHase have been mapped to the homologous region of the H-2 complex. We previously described an H-2 recombinant haplotype aw18, in which the gene for the complement component C4 and one of the two genes for 21-OHase in the H-2 class III region have been deleted. We now report that newborn aw18 homozygous mice are deficient in 21-OHase activity, and that homozygosity for the aw18 haplotype directly causes death at the early postnatal stage. Morphological changes in the adrenal glands of newborn aw18 homozygotes are also observed. The aw18 recombinant haplotype is expected to serve as a useful and, thus far, unique experimental system to study adrenal steroidogenesis in vivo and as an animal model for the inherited human disease of congenital adrenal hyperplasia.

Adrenal Glands↗