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V M Chapman

Publications and source records attributed to V M Chapman.

At least 73 records · Page 4Linked to original sources
PubMed1991

Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation.

Platelet-derived growth factor receptors are composed of two subunits (alpha and beta) that associate with one another to form three functionally active dimeric receptor species. The two subunits are encoded by separate loci in humans and other species. In this study, we used conventional interspecific backcross mapping and an analysis of a deletional mutation to establish close linkage between the alpha-subunit gene (Pdgfra) and the dominant spotting (W) locus on mouse chromosome 5. Further, by analyzing the restriction fragment length polymorphisms in interspecific F1 hybrids, we were able to demonstrate that the closely associated patch (Ph) locus carries a deletion in Pdgfra. This observation was confirmed by both DNA and RNA analysis of 10.5-day fetuses produced from crosses between Ph heterozygotes. Out of 16 fetuses analyzed, Pdgfra genomic sequences were absent and no mRNA for the receptor was detected in 6 fetuses that were developmentally abnormal (the presumptive Ph homozygotes). We also determined that the deletion associated with the Ph mutation does not extend into the coding sequences of the adjacent Kit gene, by analysis of the genomic DNA from both the interspecific F1 hybrids and the presumptive Ph homozygotes. The absence of Pdgfra genomic sequences and the lack of detectable message associated with the Ph mutation should make this mutant a valuable asset for understanding the role of the receptor alpha subunit during mammalian development.

Animals↗
PubMed1991

DNA methylation of two X chromosome genes in female somatic and embryonal carcinoma cells.

The extent of methylation of DNA sequences upstream and within the two X-linked genes, Pgk-1 and Hprt, was analyzed in male and female somatic cells and in female embryonal carcinoma cells carrying either two active X chromosomes (Xa) or one active and one inactive X chromosome (Xi). Sites upstream and within the first intron of both Pgk-1 and Hprt were heavily methylated on the Xi in somatic cells and in embryonal carcinoma cells with an Xi. Reactivation of this Xi was accompanied by extensive demethylation of these sites. In female embryonal carcinoma cells with two active X chromosomes, one X inactivates during differentiation in culture; however, methylation did not occur during differentiation, consistent with the idea that DNA methylation does not play a role in the initiation of X inactivation but may be involved in maintaining inactivation of those genes on the Xi.

Animals↗
PubMed1991

In situ analysis of centromeric satellite DNA segregating in Mus species crosses.

In situ hybridization of biotin-labeled mouse major satellite DNA clone pMR196 was applied to Mus domesticus and Mus spretus chromosomes (Chr). The same karyotypes were counterstained with distamycin A-DAPI to identify AT-rich heterochromatin. Chromosomes from the laboratory mouse, C57BL/6Ros (BL/6; M. domesticus) were uniformly labeled at the centromere except for the Y, while chromosomes from the divergent Mus species M. spretus showed little or no hybridization. Differences between Mus species in copy number of the major satellite DNA sequence were used to identify chromosomes of M. domesticus and M. spretus in their F1 hybrids and to discriminate domesticus and spretus centromeres in backcross progeny. The distribution pattern of heterochromatic regions demonstrated by distamycin A-DAPI counterstaining was comparable with that of in situ hybridization with pMR196, suggesting that A-T rich heterochromatin in M. domesticus is mainly constructed by the pMR196-related sequence. The in situ technique was used to examine segregation of domesticus centromeres in backcross progeny obtained by mating F1 hybrid females with M. domesticus or M. spretus males. The segregation of centromeres did not deviate from the expected among the backcross progeny from C57BL/6Ros males, whereas chromosomes with M. domesticus centromeres were prone to appear in the progeny from backcross matings by M. spretus males.

Animals↗
PubMed1991

Inactivation of the Rps4 gene on the mouse X chromosome.

The human RPS4X and RPS4Y genes, located on the X and Y chromosomes, appear to encode isoforms of ribosomal protein S4. Haploinsufficiency of these genes may contribute to the human phenotype known as Turner syndrome. Although RPS4X maps near the X-inactivation center, the gene is expressed on inactive human X chromosomes. We cloned Rps4, the mouse homolog of RPS4X. Exploiting allelic variation in Rps4, we examined transcription of the gene from active and inactive mouse X chromosomes in vivo, in female mice carrying an X-autosome translocation. We report that mouse Rps4, unlike human RPS4X, is subject to X inactivation. This finding may explain, at least in part, why the phenotypic consequences of X monosomy are less severe in mice than in humans.

Alleles↗
PubMed1991

Linkage of the erythroid transcription factor gene (Gf-1) to the proximal region of the X chromosome of mice.

We have used a cDNA probe for mouse Gf-1 gene that encodes the erythroid cell transcription factor to identify genetic variation in genomic DNA between Mus species. The segregation of Gf-1 DNA variation was analyzed in Mus species crosses that have been previously typed for the segregation of more than 30 genes spanning 80 cM of the mouse X chromosome from the centromere to the border of the X-Y pairing region. We identified a single X chromosome locus in the mouse, Gf-1, and an analysis of recombinants from 203 backcross progeny mapped Gf-1 to the proximal portion of the chromosome, coincident with the Cybb locus and proximal to Otc gene locus. A gene order of centromere, DXWas70, Cybb/Gf-1, Otc, Timp was established for the mouse X chromosome, which is in agreement with the map position observed on the human X chromosome.

Animals↗
PubMed1991

Linkage of amelogenin (Amel) to the distal portion of the mouse X chromosome.

Amelogenins are hydrophobic, proline-rich proteins that are the primary biosynthetic products of ameloblasts. These cells are responsible for the formation of tooth enamel, and amelogenins play an important role in the process of biomineralization. A cDNA, corresponding to the mouse 26-kDa amelogenin, has been molecularly cloned and sequenced. Southern blot analysis of genomic DNA from the mouse using this cDNA as a probe indicates that there is only one mouse amelogenin (Amel) gene. This paper describes restriction site variation for the Amel gene that we have identified between C57BL/6 and M. spretus and the segregation of that variation as an X-chromosome gene. The position of the amelogenin locus (Amel) relative to the loci for alpha-galactosidase (Ags), proteolipoprotein (Plp), and the random genomic probe DXWas31 has been determined. Amel is established as: (1) the most distal locus in the genetic map of the mouse X chromosome, (2) lying proximal to the X:Y pairing region, and (3) being restricted to the mouse X chromosome.

Amelogenin↗
PubMed1991

Linkage of loci associated with two pigment mutations on mouse chromosome 13.

Progeny from one intra- and two inter-specific backcrosses between divergent strains of mice were typed to map multiple markers in relation to two pigment mutations on mouse chromosome 13, beige (bg) and pearl (pe). Both recessive mutants on a C57BL/6J background were crossed separately with laboratory strain PAC (M. domesticus) and the partially inbred M. musculus stock PWK. The intra- and inter-specific F1 hybrids were backcrossed to the C57BL/6J parental strain and DNA was prepared from progeny. Restriction fragment length polymorphisms were used to follow the segregation of alleles in the backcross offspring at loci identified with molecular probes. The linkage analysis defines the association between the bg and pe loci and the loci for the T-cell receptor gamma-chain gene (Tcrg), the spermatocyte specific histone gene (Hist1), the prolactin gene (Prl), the Friend murine leukaemia virus integration site 1 (Fim-1), the murine Hanukuh Factor gene (Muhf/Ctla-3) and the dihydrofolate reductase gene (Dhfr). This data confirms results of prior chromosomal mapping studies utilizing bg as an anchor locus, and provides previously unreported information defining the localization of the prolactin gene on mouse chromosome 13. The relationship of multiple loci in relation to pe is similarly defined. These results may help facilitate localization of the genes responsible for two human syndromes homologous with bg and pe, Chediak-Higashi syndrome and Hermansky-Pudlak syndrome.

Animals↗
PubMed1991

Detailed genetic mapping of the A-raf proto-oncogene on the mouse X chromosome.

The transcribed murine A-raf proto-oncogene has been localized to the proximal region of the mouse X chromosome, within the context of four other active genes in this region which together constitute a conserved linkage group between mouse and man. This localization has been accomplished using species-specific restriction fragment length variation and DNAs from a previously defined informative subset of progeny representative of a set of 100 progeny from an interspecific backcross between inbred C57BL/6JRos and wild-derived Mus spretus. This new data regionally orders the mouse A-raf locus relative to the 24 X-linked markers previously examined in this backcross. We find that A-raf co-localizes with two other active genes, tissue inhibitor of metalloproteinases (Timp) and synapsin (Syn-1), 4.0 +/- 2.0 cM distal to the Otc gene at the proximal end of the mouse X chromosome, for a partial gene order in this region of: centromere-Cybb-Otc-Timp/A-raf/Syn-1-Xlr-1-Hprt.

Animals↗
PubMed1990

Comparison of baseline sister-chromatid exchanges (SCE), cyclophosphamide-, ethylnitrosourea (ENU)-induced SCE, ENU-induced cell-cycle delay and chromosome aberrations between Peru and laboratory mice.

The baseline sister-chromatid exchange (SCE) frequency and sensitivity to the effects of the mutagens cyclophosphamide (CPP) and ethylnitrosourea (ENU) in bone-marrow cells of descendants of wild mice trapped from Rimac valley in Peru (Peru mice) were studied and compared to the same effects in laboratory mice. Baseline SCE of the Peru mice were significantly higher than those of the C57BL/6J and DBA/2 mice. The average SCE/cell of 4 Peru mice was 5.4 (range 3.8-7.6), while the average of SCE/cell of either 4 C57BL or 5 DBA mice was 3.2 (range 3.0-3.4). The variation of SCE/cell among Peru mice studied was statistically significant whereas among C57BL or DBA mice it was not. SCE frequencies of primary cultures derived from the ear tissue of 10 Peru (mean SCE/cell = 8.5) were also significantly higher than those of 6 C57BL mice (mean SCE/cell = 7.4). CPP treatment resulted in a dose-dependent increase of SCE frequencies in bone-marrow cells of all the mice. However, some of Peru mice treated with CPP had significantly higher SCE than the other Peru mice and than all of the C57BL and DBA mice treated with equivalent dose. ENU induced increased SCE frequencies in Peru and C57BL mice. Again some of Peru mice either had significantly higher SCE, greater extent induced cell-cycle delay or chromosome aberrations (CA) than other Peru mice and than of all the C57BL mice treated with equivalent dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Linkage of a gene for neural cell adhesion molecule, L1 (CamL1) to the Rsvp region of the mouse X chromosome.

L1 is a glycoprotein with an apparent molecular weight of 200 kDa in the developing fetus and adult central nervous system. In the peripheral nervous system, it has a molecular weight of 230 kDa. The L1 protein appears to be encoded by a single gene that has been located on the human X chromosome by in situ hybridization. In this paper we describe restriction variation in genomic DNA Southern analysis between Mus species for the K13 cDNA probe for the L1 neural cell adhesion molecule. We have designated the locus described by this variation as cell adhesion molecule L1, CamL1. The X chromosome linkage and the relative position on the X chromosome coincident with the genes Rsvp/G6pd/Cf-8 were defined in backcross matings involving M. spretus and M. musculus.

Animals↗
PubMed1990

Efficient linkage of 10 loci in the proximal region of the mouse X chromosome.

Interspecific Mus species crosses were used to construct a multilocus genetic map of the mouse X chromosome that extends for more than 50 cM. In these studies, we established the segregation of eight loci in more than 200 backcross progeny from crosses of M. musculus and M. spretus with a common inbred strain (C57BL/6JRos). Genetic divergence at the level of the nucleotide sequences makes these crosses a useful cumulative genetic resource for mapping additional genes defined by genomic or cDNA probes in a highly efficient manner. We have therefore devised a mapping strategy that uses a subset of these backcrosses that are recombinant between successive anchor loci to both localize and order an additional set of six genes without necessarily resorting to an analysis of the entire backcross series. Using this approach, we have defined the linkage of cytochrome b245 beta-chain (Cybb), synapsin (Syn-1), and two members of the X-linked lymphocyte-regulated gene family (Xlr-1, Xlr-2), as well as DXSmh141 and DXSmh172, two loci defined by random genomic probes. All six loci have been localized to the proximal portion of the mouse X chromosome and their order has been defined as Cybb, Otc, Syn-1/Timp, DXSmh141/Xlr-1, DXSmh172, Hprt, Xlr-2, Cf-9. Gene order was established by minimizing multiple recombination events across the region spanning an estimated 20 cM of the proximal X chromosome. The possible significance of the Xlr loci is discussed with respect to other X-chromosome loci that regulate the immune response.

Animals↗
PubMed1990

Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2.

A series of overlapping cDNAs coding for mouse prothrombin (coagulation factor II) have been isolated and the composite DNA sequence has been determined. The complete prothrombin cDNA is 1,987 bp in length [excluding the poly(A) tail] and codes for 18 bp of 5' untranslated sequence, an open reading frame coding for 618 amino acids, a stop codon, and a 3' untranslated region of 112 bp followed by a poly(A) tail. The translated amino acid sequence predicts a molecular weight of 66,087, which includes 10 residues of gamma-carboxyglutamic acid. There are five potential N-linked glycosylation sites. Mouse prothrombin is 81.4% and 77.3% identical to the human and bovine proteins, respectively. Comparison of the cDNA coding for mouse prothrombin to the human and bovine cDNAs indicates 79.9% and 76.5% identity, respectively. Amino acid residues important for the structure and function of human prothrombin are conserved in the mouse and bovine proteins. In the adult mouse and rat, prothrombin is primarily synthesized in the liver, where is constitutes 0.07% of total mRNA as determined by solution hybridization analysis. The genetic locus for mouse prothrombin, Cf-2, has been mapped using an interspecies backcross and DNA fragment differences between the two species. The prothrombin locus lies on mouse chromosome 2, 1.8 +/- 1.3 map units proximal to the catalase locus. The gene order in this region is Cen-Acra-Cf-2-Cas-1-A-Tel. This localization extends the proximal boundary of the known region of homology between mouse chromosome 2 and human chromosome 11p from Cas-1 about 2 map units toward the centromere.

Amino Acid Sequence↗
PubMed1990

Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome.

A mouse cDNA probe homologous to the human MCF2 transforming sequence has been identified and partially cloned, and is used here to localize the gene on the mouse X chromosome. The human gene has been physically mapped to within 60 kb of the gene for coagulation factor IX, within a large conserved linkage group between the mouse and human genomes which extends from HPRT to G6PD on the X chromosomes of both mammalian species. In situ hybridization of the mouse Mcf-2 probe onto mouse metaphase chromosomes indicates that this gene lies in the same region of the X chromosome as Cf-9, the mouse gene for coagulation factor IX. Moreover, segregation of species-specific genomic DNA polymorphisms for Mcf-2 and Cf-9 in a total of 203 individuals derived from two large interspecific mouse backcross populations (which are also segregating for 17 other X-linked molecular markers) demonstrates that the mouse genes are separated by only 0.5 +/- 0.5 cM. Despite this short distance we were able to order Mcf-2 and Cf-9 relative to one another and other genes in this region. The mouse gene order Hprt-Cf-9-Mcf-2-G6pd predicts a similar ordering of genes on the human X chromosome, a gene order which has only recently been demonstrated by physical mapping. Thus, the map location and linkage relationships of the Mcf-2 gene are similar in man and mouse, and this unique protooncogenic locus is part of a conserved linkage group on the mammalian X chromosome.

Animals↗
PubMed1989

Comparison of the physical and recombination maps of the mouse X chromosome.

The locations of five random mouse genomic DNA markers and five cloned genes, including the genes for clotting factors VIII and IX (Cf-8 and Cf-9), Duchenne muscular dystrophy (Dmd), phosphoglycerate kinase-1 (Pgk-1), and alpha-galactosidase (Ags), on the mouse X chromosome were determined by in situ hybridization. The five random DNA markers provide new genetic loci with useful restriction fragment length polymorphisms between mouse strains and species, including one locus close to the centromeric region of the mouse X chromosome. The physical map and the recombination map of these loci on the X chromosome were compared. There was good agreement in the order of loci. Relative distances between loci were consistent along the X chromosome, with the exception of the telomeric end of the long arm, where the recombination fraction observed between loci closely associated on the physical map was higher than that between similarly spaced markers located in the proximal region of the X chromosome. These results are discussed in comparison to the human X-chromosome map.

Animals↗
PubMed1989

Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice.

We have used elevated levels of plasma creatine phosphokinase activity to identify muscular dystrophy phenotypes in mice and to screen the progeny of chemical mutagen-treated male mice for X chromosome-linked muscular dystrophy mutations. We were not successful in identifying heterozygous carriers of these induced muscular dystrophy mutations in greater than 8000 progeny. However, we were highly successful in identifying three additional alleles of the characterized mdx locus. These alleles of mdx were recovered from various mutagen-treated males and they occur on an X chromosome that carries flanking markers that allow us to follow the mutations in genetic crosses and in the development of corresponding mutant stocks. These alleles have been designated as mdx2Cv, mdx3Cv, and mdx4Cv. Preliminary data show that mice with mdx2Cv and mdx3Cv mutations have muscular dystrophic phenotypes that do not grossly differ from the characterized mdx mutation. These additional mdx mutations expand the value of mouse models of X chromosome-linked muscular dystrophy and potentially define additional sites of mutation that impair dystrophin expression.

Animals↗
PubMed1988

The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus.

Mice carrying mutations at the W locus located on chromosome 5 are characterized by severe macrocytic anaemia, lack of hair pigmentation and sterility. Mutations at this locus appear to affect the proliferation and/or migration of cells during early embryogenesis and result in an intrinsic defect in the haematopoietic stem cell hierarchy. An understanding of the molecular basis of the complex and pleiotropic phenotype in W mutant mice would thus provide insights into the important developmental processes of gametogenesis, melanogenesis and haematopoiesis. Here we show that the mouse mutant W has a deletion of the c-kit proto-oncogene. Interspecific backcross analysis demonstrates that the W locus is very tightly linked to c-kit and that the two loci cannot be segregated at this level of analysis. c-kit is the cellular homologue of the oncogene v-kit of the HZ4 feline sarcoma virus and encodes a transmembrane protein tyrosine kinase receptor that is structurally similar to the receptors for colony-stimulating factor-1 (CSF-1) and platelet derived growth factor. The co-localization of c-kit with W provides a molecular entry into this important region of the mouse genome. In addition, these observations provide the first example of a germ-line mutation in a mammalian proto-oncogene and implicate the c-kit gene as a candidate for the W locus.

Animals↗
PubMed1988

Altered turnover of allelic variants of hypoxanthine phosphoribosyltransferase is associated with N-terminal amino acid sequence variation.

The results of our previous studies suggested that differences in the primary structures of the hypoxanthine phosphoribosyltransferase (HPRT) A and B proteins (EC 2.4.2.8) of mice are associated with altered turnover of these proteins in reticulocytes. On the basis of nucleotide sequence comparisons of their corresponding cDNAs, we show here that the HPRT A and B proteins differ at two positions; there is an alanine/proline substitution at amino acid position 2 and a valine/alanine substitution at amino acid position 29 (HPRT A/B proteins, respectively; total protein length, 218 amino acids). On the basis of results obtained from sequencing of the N termini of the purified HPRT A and B proteins, we also show that these amino acid substitutions are associated with differences in processing of the proteins; HPRT B, which is encoded as N-terminal Met-Pro, has a free N-terminal proline residue; HPRT A, which is encoded as N-terminal Met-Ala, lacks a free N-terminal alpha-amino group and is presumed to be acetylated following removal of the N-terminal methionine (i.e. AcO-Ala). These observations are discussed in reference to the idea that the N terminus of a protein plays a role in determining the rate at which the protein is degraded in erythroid cells.

Alleles↗