Assignment of the gene coding for HPRT enzyme to Syrian hamster X chromosome by microcell fusion.
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Animals↗
Biomedical subjects
G Levan
Publications and source records attributed to G Levan.
Characterization and mapping of a highly conserved processed pseudogene and an intron-carrying gene of the heat shock cognate protein 70 (Hsc70) gene family in the rat.
A processed pseudogene of the rat Hsc70 gene, Hsc70-ps1, is described, which still presents the open reading frame of the original gene. The pseudogene does not appear to be expressed. It maps to rat Chromosome (Chr) 2. The intron-carrying Hsc70 gene localizes to Chr 8. Hsc70-specific probes detect a large number of more than 20 cross-hybridizing fragments, which show only limited length polymorphism among various inbred rat strains.
Animals↗
Standardized rat genetic nomenclature.
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Animals↗
Loss of expression of basement membrane proteins reflects anomalies of chromosomes 3 and 12 in the rat 4-nitroquinoline-N-oxide model of oral carcinogenesis.
This study examined the cytogenetic characteristics of keratinocyte cell lines derived from rat oral tissues treated in vivo with the carcinogen 4-nitroquinoline-N-oxide. A parent tumour with a spectrum of differentiation was used to establish clonal subpopulations that formed differentiated (squamous cell carcinomas; SCCs) and undifferentiated (spindle cell phenotype) tumours following transplantation to athymic mice. By contrast to spindle cell tumours, SCCs elaborated basement membrane proteins (laminin and collagen IV). Both diploid and tetraploid subpopulations formed either SCCs or spindle cell tumours. An unbalanced 10q+ translocation was common to all cell lines. Anomalies of chromosomes 3 and 12 (gain, loss, deletions, translocations) were present only in cell lines that formed spindle cell tumours and were absent in keratinocytes forming SCCs. The results suggest that proto-oncogenes and/or tumour suppression genes located to rat chromosomes 3 and 12 may control tumour cell differentiation.
3T3 Cells↗
Colcemid resistance in murine SEWA cells: non-Pgy gene amplification at low levels of resistance and preferential Pgy2 gene amplification at high levels of resistance.
Mammalian cell lines often become multidrug-resistant to cytotoxic drugs by amplification and/or overexpression of the P-glycoprotein (Pgy) genes. However, several malignant cell lines seem to acquire low levels of drug resistance by non-P-glycoprotein mediated mechanisms. We report here on cytogenetical signs of non-Pgy gene amplification in murine SEWA cells during the early steps of selection in Colcemid (COL). In line TC13COL0.01, rare cells exhibited a homogeneously staining region (HSR) distally in chromosome 16. As the COL-concentration was raised the HSR-chromosome was retained and, in addition, the cells developed numerous double minutes (DMs). The DMs, but not the HSR, contained amplified Pgy genes. The HSR may correspond to amplified heat shock protein 70 (Hsp70) genes, detected by Southern analysis. A second low-level COL-resistant line, TC13D70.01, contained DMs but showed no amplification of Pgy, Hsp70, Hsp90, alpha- or beta-tubulin genes. In higher COL-concentration, P-glycoprotein mediated drug resistance was induced. In contrast to actinomycin D-resistant SEWA cells, in which higher amplification levels of Pgy1 than of Pgy2 are regularly present, the COL-resistant lines showed a preference for Pgy2 gene amplification. These results are in line with the suggestion that the murine Pgy1 and Pgy2 genes have overlapping but distinct drug specificities.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
C-band-positive double minutes have kinetochore proteins.
Double minutes (DMs) have been shown generally to lack centromeres. In the present paper we report on C-band-positive DMs in Colcemid-resistant SEWA cells. These DMs were heavily labeled after in situ hybridization with mouse major satellite DNA and, furthermore, reacted positively with antikinetochore antibodies. Upon antikinetochore antibody labeling, the immunofluorescent signals of some DMs were strong, indicating that they had functional centromeres.
Animals↗
Localization of the genes encoding the three rat angiotensin II receptors, Agtr1a, Agtr1b, Agtr2, and the human AGTR2 receptor respectively to rat chromosomes 17q12, 2q24 and Xq34, and the human Xq22.
Using fluorescence in situ hybridization, we determined the regional localization of the 3 rat genes encoding angiotensin II receptors at 17q12 (Agtr1a), 2q24 (Agtr1b) and Xq34 (Agtr2). In parallel, we showed that the type 2 human gene, AGTR2, also maps on the X chromosome, at band Xq22.
Animals↗
Cloning of a parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) cDNA from a rat osteosarcoma (UMR 106) cell line: chromosomal assignment of the gene in the human, mouse, and rat genomes.
Complementary DNAs spanning the entire coding region of the rat parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) were isolated from a rat osteosarcoma (UMR 106) cell-line cDNA library. The longest of these clones (rPTHrec4) was used to chromosomally assign the PTHR gene in the human, rat, and mouse genomes. By somatic cell hybrid analysis, the gene was localized to human chromosome 3 and rat chromosome 8; by in situ hybridization, the gene was mapped to human chromosome 3p21.1-p22 and to mouse chromosome 9 band F; and by interspecific backcross analysis, the Pthr gene segregated with the transferrin (Trf) gene in chromosome 9 band F. Mouse chromosome 9 and rat chromosome 8 are known to be highly homologous and to also show synteny conservation with human chromosome 3. These three chromosomes share the transferrin gene (TF), the myosin light polypeptide 3 gene (MYL3), and the acylpeptide hydrolase gene (APEH). Our results add a fourth gene, the PTHR gene, to the synteny group conserved in these chromosomes.
Animals↗
Chromosomal assignment of four genes encoding Na/H exchanger isoforms in human and rat.
The plasma membrane Na/H exchanger plays an essential role in regulating intracellular pH and Na+ concentration and has been implicated in several pathophysiological conditions, including essential hypertension and congenital secretory diarrhea. Four isoforms of the Na/H exchanger encoded by separate genes have recently been identified by cDNA cloning. To map their locations in the human and rat genomes, rat isoform-specific cDNA probes were hybridized to Southern filters containing panels of somatic cell hybrids that segregate either human or rat chromosomes. The rat Nhe1 gene was assigned to Chromosome (Chr)5, extending the homology with human chromosome 1p that has previously been shown to contain the human NHE1 gene. The genes encoding the NHE-2 and NHE-4 isoforms were syntenic in the two species and assigned to rat Chr 9 and human Chr 2. A single Nhe3 gene was detected in rat and assigned to Chr 1. In contrast, although evidence to date has suggested a single human NHE3 gene on Chr 5, two NHE3 genes, NHE3A and NHE3B, were identified and assigned to Chrs 10 and 5, respectively. Interestingly, rat Chr 1 has recently been found to carry a gene controlling systolic blood pressure upon sodium loading in stroke-prone, spontaneously hypertensive rats. Thus, this and other evidence implicates rat Nhe3 as a possible candidate gene in this disease process.
Animals↗
Assignment of rat Jun family genes to chromosome 19 (Junb), chromosome 5q31-33 (Jun), and chromosome 16 (Jund).
By means of somatic cell hybrids segregating rat chromosomes, we determined the chromosome localization of three rat genes of the Jun family: Junb (Chr 19), Jun (=c-Jun) (Chr 5) and Jund (Chr 16). The Jun gene was also localized to the 5q31-33 region by fluorescence in situ hybridization. These rat gene assignments reveal two new homologies with mouse and human chromosomes, and provide a new example of synteny conserved in the human and a rodent species (the mouse), but split between the two rodent species.
Animals↗
A novel, conserved gene of the rat that is developmentally regulated in the testis.
From a rat testis library three overlapping cDNA clones were isolated that represent a novel single-copy gene, designated Tegt. Two transcripts of 2.8 and 1.0 kb were found in each organ tested. The shorter transcript was highly abundant in adult testis. A similar expression pattern was found in the mouse. Analysis of rat RNA from different stages of spermatogenesis indicated that accumulation of the short transcript occurred mainly postmeiotically. The rat Tegt gene maps to Chromosome (Chr) 7, and its mouse homolog to Chr 15.
Aging↗
Drug-specific rearrangements of chromosome 12 in hydroxyurea-resistant mouse SEWA cells: support for chromosomal breakage model of gene amplification.
In order to investigate whether specific, nonrandom chromosome rearrangements were involved in the induction of hydroxyurea (HU) resistance in mouse SEWA cells, we undertook detailed cytogenetic analyses of three independently selected lines during the long-term treatment with HU. We found that cells with trisomy 12 had selective advantage during early steps of HU treatment. Subsequently, numerous rearrangements of chromosome 12 took place in each of the HU-resistant cell lines. More specifically, the proximal end of chromosome 12 (band A3) was frequently involved in breaks and fusions generating multicentric marker chromosomes. In situ hybridization showed that the functional Rrm2 gene was located in this particular region of chromosome 12. Furthermore, amplification and rearrangements of the structural gene Rrm2 were detected both at the chromosomal and at the molecular level. As discussed, the results of the cytogenetic analyses support the chromosomal breakage model of gene amplification.
Animals↗
Decidual prolactin-related protein. Identification, molecular cloning, and characterization.
In this report, we describe the isolation, molecular cloning, and characterization of a new member of the prolactin (PRL)-growth hormone (GH) family expressed in rat decidual tissue. A 29-kDa protein was isolated from medium conditioned by decidual explants. The protein possessed an affinity for concanavalin A and cross-reactivity with antibodies to two rat placental proteins, PRL-like protein-B (PLP-B) and PLP-C and with antibodies to human PRL. NH2-terminal sequencing of the isolated decidual protein indicated that it shared significant sequence identity with the NH2 terminus of PLP-C. The decidual protein was termed decidual prolactin-related protein (dPRP). A PLP-C cDNA was used to identify dPRP cDNAs from a rat decidual cDNA library. Nucleotide sequence analyses of the dPRP cDNAs predicted a mature protein of 239 amino acids, including a 28-amino acid signal sequence. The predicted dPRP amino acid sequence contains two putative N-linked glycosylation sites and 6 cysteine residues. The 6 cysteines are located in positions homologous to the cysteines of PLP-C and PRL. Additional sequence similarities with members of the PRL-GH family are evident. The dPRP gene was localized to rat chromosome 17, which also carries other members of the PRL gene family. Northern blot analysis showed that the dPRP cDNA clone specifically hybridized to a 1.0-kilobase mRNA. The relationship of dPRP with other members of the PRL-GH family and its putative role(s) in the physiology of pregnancy are discussed.
Amino Acid Sequence↗
Universal mapping probes and the origin of human chromosome 3.
Universal mapping probes (UMPs) are defined as short segments of human DNA that are useful for physical and genetic mapping in a wide variety of mammals. The most useful UMPs contain a conserved DNA sequence immediately adjoined to a highly polymorphic CA repeat. The conserved region determines physical gene location, whereas the CA repeat facilitates genetic mapping. Both the CA repeat and its neighboring sequence are highly conserved in evolution. This permits molecular, cytogenetic, and genetic mapping of UMPs throughout mammalia. UMPs are significant because they make genetic information cumulative among well-studied species and because they transfer such information from "map rich" organisms to those that are "map poor." As a demonstration of the utility of UMPs, comparative maps between human chromosome 3 (HSA3) and the rat genome have been constructed. HSA3 is defined by at least 12 syntenic clusters located on seven different rat chromosomes. These data, together with previous comparative mapping information between human, mouse, and bovine genomes, allow us to propose a distinct evolutionary pathway that connects HSA3 with the chromosomes of rodents, artiodactyls, and primates. The model predicts a parsimonious phylogenetic tree, is readily testable, and will be of considerable use for determining the pathways of mammalian evolution.
Animals↗
Assignment of the chromogranin A (Chga) locus to homologous regions on mouse chromosome 12 and rat chromosome 6.
Chromogranin A is an acidic protein, stored and released with catecholamines, and is overexpressed in genetic hypertension. In the human genome, its locus has previously been positioned on the long arm of Chromosome 14 in the 14q32 region. As a first step toward evaluating its potential linkage with hereditary hypertension, we determined its chromosomal position in mouse and rat. Chromogranin A was present as a single-copy gene in both mouse and rat. Analysis of the allele distribution in an interspecific mouse backcross by single-strand conformation polymorphism positioned the chromogranin A locus on Chromosome 12, between Igh-C and D12Pas1. Evaluation of a rat/mouse somatic cell hybrid panel indicated that chromogranin A is on rat Chromosome 6. In each case (mouse, rat, and human), chromogranin A is in a conserved region with nearby markers including the immunoglobulin heavy chain locus.
Animals↗
Assignment of 22 loci in the rat by somatic hybrid and linkage analysis.
Twenty structural genes and two unique anonymous DNA fragments have been mapped in the rat (Rattus norvegicus) with a panel of mouse x rat hybrids and linkage analysis. Ten of the 20 autosomes are represented by at least one of these markers. A new syntenic relationship among rat Chromosome (Chr) 16, mouse Chr 14, and human Chr 10q was established. Results of this study further support the extensive conservation of synteny between the rat and mouse and, to a lesser degree, between rat and human.
Animals↗
Chromosomal assignment of seven rat homeobox genes to rat chromosomes 3, 4, 7, and 10.
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Animals↗
Assignment of the rat genes coding for dopa decarboxylase (DDC) and glutamic acid decarboxylases (GAD1 and GAD2).
By use of rat cDNA probes and a panel of cell hybrids segregating rat chromosomes, the genes encoding three pyridoxal 5'-phosphate (PLP)-dependent decarboxylases--namely, DOPA-decarboxylase (Ddc), glutamic acid decarboxylase 1 and 2 (Gad1 and Gad2)--were assigned to rat Chromosomes (Chrs) 14, 3, and 17, respectively. If one takes into account chromosome localizations in the human and the mouse, the present results (i) show that a synteny group is retained on rat Chr 14, human Chr 7, and mouse Chr 11 (Ddc); (ii) strengthen the homology relation known between rat Chr 3 and human and mouse Chrs 2 (Gad1); (iii) suggest that rat Chr 17 has no extensive homology to any human chromosome; and (iv) suggest the order (Prl, Fdp)--Tpl2--Gad2 on the rat Chr 17.
Animals↗