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V M Chapman

Publications and source records attributed to V M Chapman.

At least 91 records · Page 5Linked to original sources
PubMed1988

Multilocus molecular mapping of the mouse X chromosome.

Using restriction fragment length polymorphisms (RFLPs) and enzymatic variants between distantly related mouse species, we have assigned three genes to the mouse X chromosome and concurrently mapped a total of eight genes spanning an estimated 50 cM of the chromosome. Segregation of RFLPs in over 200 male progeny from interspecies backcrosses between the inbred strain C57BL/6JRos and either wild-derived Mus musculus or Mus spretus was followed for the murine genes Timp (tissue inhibitor of metalloproteinases), Cf-8 (coagulation factor VIII), and Rsvp (red-sensitive visual pigment) and the known X-linked markers Otc, Hprt, Cf-9, G6pd, and Ags. From the centromere, the gene order was defined as Otc, Timp, Hprt, Cf-9, (Cf-8/Rsvp/G6pd), Ags, by minimizing the number of multiple recombinational events. No significant differences in map order or frequency of recombination were observed between the two backcross series studied. The use of Southern analysis has allowed us to add new genes to the map in a cumulative manner, and as probes become available, additional markers can be mapped, using the same set of mice, by utilizing existing blots or resampling the DNAs. The use of probes for functional genes has allowed us to directly compare the X chromosomes of mouse and man and has provided insight into chromosomal rearrangements which have occurred during the evolutionary divergence of these species, as well as to define the extent of linkage homologies.

Animals↗
PubMed1987

Abnormal subcellular distribution of beta-glucuronidase in mice with a genetic alteration in enzyme structure.

Liver beta-glucuronidase is structurally altered in inbred strain PAC so that a peptide subunit with a more basic isoelectric point, GUS-SN, is produced. This allele of beta-glucuronidase was transferred to strain C57BL/6J by 12 backcross matings to form the congenic line B6 X PAC-Gus(n). Liver beta-glucuronidase activity was halved in males of the congenic strain compared to normal males. The lowered activity was specifically accounted for by a decrease in the lysosomal component. There was no alteration in the concentration of microsomal activity. This alteration in the subcellular distribution of beta-glucuronidase in Gus(n)/Gus(n) mice was confirmed by two independent gel electrophoretic systems which separate microsomal and lysosomal components. beta-Glucuronidase activity was likewise approximately halved in mutant spleen, lung, and brain, organs which contain exclusively or predominantly lysosomal beta-glucuronidase. The loss of liver lysosomal beta-glucuronidase activity was shown by immunotitration to be due to a decrease in the number of beta-glucuronidase molecules in lysosomes of the congenic strain. The Gus(n) structural alteration likely causes the lowered lysosomal beta-glucuronidase activity since the two traits remain in congenic animals. Heterozygous Gus(n)/Gus(b) animals had intermediate levels of liver beta-glucuronidase. Also, the effect was specific, in that three other lysosomal enzymes were not reproducibly lower in Gus(n)/Gus(n) mice. Gus(n) is, therefore, an unusual example of a mutation which causes a change in the subcellular distribution of a two-site enzyme.

Animals↗
PubMed1987

Regional localization of the murine Duchenne muscular dystrophy gene on the mouse X chromosome.

The murine locus corresponding to the human Duchenne/Becker muscular dystrophy (DMD) gene has been regionally mapped on the mouse X chromosome by hybridizing DNA from interspecies mouse crosses with a cDNA clone for the mouse Dmd gene. The results demonstrate that the relative organization of genes on the murine and human X chromosomes is more divergent than has previously been postulated. Furthermore, the mouse Dmd gene maps to a similar region of the X chromosome as does the mouse muscular dystrophy mutation mdx, providing further evidence that the mdx mutant may be a murine equivalent of human DMD. However, Southern analysis of portions of the mouse Dmd gene has not yet revealed any differences between mdx and wild-type mice.

Animals↗
PubMed1987

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)

Alleles↗
PubMed1987

Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse.

We have examined the relative methylation levels of several dispersed repeated and low-copy-number gene sequences during gametogenesis and early embryogenesis. Southern blot analyses revealed that L1, intercisternal A particle (IAP), and major urinary protein (MUP) sequences were undermethylated extensively at MspI sites in DNA from diplotene oocytes. In contrast, the same sequences were highly methylated in DNA from pachytene spermatocytes, round spermatids, and epididymal sperm. These results indicate that there are genome-wide DNA methylation differences between oogenesis and spermatogenesis. Repeated sequences in DNA from cleavage-stage embryos and inner cell masses (ICM) were methylated at intermediate levels, consistent with transient maintenance of gametic methylation levels during early embryogenesis. Gametic differences in DNA methylation observed here indicate that methylation could provide a mechanism for imprinting maternal and paternal genomes resulting in differential regulation of parental genomes during early development.

Animals↗
PubMed1986

Undermethylation of structural gene sequences in extraembryonic lineages of the mouse.

The first two lineages to differentiate in the mouse embryo are the trophectoderm and primitive endoderm, which give rise to various extraembryonic structures only. Previous work has shown that all derivatives of these two lineages share the property of undermethylation of repetitive DNA sequences, both satellite and dispersed. Here we show that this undermethylation is not a peculiarity of these repetitive elements but is also a feature of structural gene sequences within both lineages. alpha-Fetoprotein, albumin, and major urinary protein gene sequences all showed extensive undermethylation at MspI restriction sites in extraembryonic lineages, which did not correlate with their expression in these tissues. The same sequences were heavily methylated in embryonic tissues as early as 7.5 days of development. There are, therefore, major global differences in DNA methylation between the earliest cell lineages to be established in the mouse embryo. The significance of these differences for cellular commitment events remains to be elucidated.

Albumins↗
PubMed1985

Elevated levels of erythrocyte hypoxanthine phosphoribosyltransferase associated with allelic variation of murine Hprt.

Murine stocks with wild-derived hypoxanthine phosphoribosyltransferase (HPRT) A alleles (Hprt a) have erythrocyte HPRT activity levels that are approximately 25-fold (Mus musculus castaneus) and 70-fold (Mus spretus) higher than those of laboratory strains of mice with the common Hprt b allele (Mus musculus: C3H/HeHa or C57B1/6). Since the purified HPRT A and B enzymes have substantially similar maximal specific activities (64 and 46 units/mg of protein, respectively), we infer that these HPRT activity levels closely approximate the relative levels of HPRT protein in these cells. Red blood cells of HPRT A and B mice have similar levels of adenine phosphoribosyltransferase activity (APRT; EC 2.4.2.7) and reticulocyte percentages, which suggests that the elevated levels of HPRT in erythrocytes of HPRT A mice are not secondary consequences of abnormal erythroid cell development. The HPRT activity levels in reticulocytes of HPRT B mice are approximately 35-fold higher than the levels in their erythrocytes and approach the HPRT activity levels in reticulocytes of HPRT A mice. Thus, the marked differences in the levels of HPRT protein in erythrocytes of HPRT A and B mice result from differences in the extent to which the HPRT A and B proteins are retained as reticulocytes mature to erythrocytes. The substantial and preferential loss of HPRT B activity from reticulocytes is paralleled by an equivalent loss of HPRT immunoreactive protein (i.e., CRM) from that cell, and we infer that the HPRT B protein is degraded or extruded as reticulocytes mature to erythrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1984

Biochemical diversity and evolution in the genus Mus.

Thirteen biochemical groups of wild mice from Europe, Asia, and Africa belonging to the genus Mus are analyzed at 22-42 protein loci. Phylogenetic trees are proposed and patterns of biochemical evolution are discussed, as well as the possible contribution of wild mice to the genetic diversity of laboratory stocks.

Alleles↗
PubMed1983

Construction of a small Mus musculus repetitive DNA library: identification of a new satellite sequence in Mus musculus.

We report the construction of a small library of recombinant plasmids containing Mus musculus repetitive DNA inserts. The repetitive cloned fraction was derived from denatured genomic DNA by reassociation to a Cot value at which repetitive, but not unique, sequences have reannealed followed by exhaustive S1 nuclease treatment to degrade single stranded DNA. Initial characterizations of this library by colony filter hybridizations have led to the identification of a previously undetected M. musculus minor satellite as well as to clones containing M. musculus major satellite sequences. This new satellite is repeated 10-20 times less than the major satellite in the M. musculus genome. It has a repeat length of 130 nucleotides compared with the M. musculus major satellite with a repeat length of 234 nucleotides. Sequence analysis of the minor satellite has shown that it has a 29 base pair region with extensive homology to one of the major satellite repeating subunits. We also show by in situ hybridization that this minor satellite sequence is located at the centromeres and possibly the arms of at least half the M musculus chromosomes. Sequences related to the minor satellite have been found in the DNA of a related Mus species, Mus spretus, and may represent the major satellite of that species.

Animals↗
PubMed1983

Interspecific hybrids and chimeras in mice.

Interspecific hybrids and chimeras in mammals provide unique tools for investigating problems in genetics and embryology, because of the degree of disparity between the two component genotypes. We have attempted to produce hybrids and chimeras between Mus musculus, the laboratory mouse, and Mus caroli, a wild species of mouse from Southeast Asia. M. musculus and M. caroli do not normally interbreed, although sterile hybrids can be produced at a low rate by artificial insemination. Extrinsic problems of genotypic incompatibility between the fetus and the maternal environment seem to be involved in poor hybrid survival, since M. caroli blastocysts also die when transferred to the M. musculus uterus. Death is associated with the generation of maternal T-cells which are cytotoxic to M. caroli target cells in vitro. It is not yet clear whether this immune response is the primary cause of death or is secondary to breakdown of some other components of the fetal-maternal interaction. It is clear, however, that it is the trophoblast layer that mediates survival or death of the foreign embryonic cells in the M. musculus juterus, since M. caroli inner cell mass cells can survive to term after injection into M. musculus blastocysts: Viable interspecific chimeras result. Even more convincing evidence is provided by the production of viable M. caroli offspring by trophoblast vesicle reconstitution using trophoblast of M. musculus genotype and inner-cell mass of M. caroli type. Studies of properties of isolated trophoblast tissues have indicated that M. caroli trophoblast may differ from M. musculus in both its antigenic and immunosuppressive properties. Elucidation of trophoblast-uterine interactions in these various interspecific pregnancies is being aided by the development of an in situ marker system, which can distinguish cells of the two species in sectioned material by in situ hybridization with a M. musculus satellite DNA probe. This same marker is also proving a very powerful tool for analyzing cell lineage development in chimeras.

Animals↗