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J Szpirer

Publications and source records attributed to J Szpirer.

At least 19 recordsLinked to original sources
PubMed1996

Dispersion of chromogranin/secretogranin secretory protein family loci in mammalian genomes.

Chromogranin A, chromogranin B, and secretogranin II, members of the chromogranin/secretogranin secretory protein family, are overexpressed in some human hereditary maladies and may have arisen, in part, from common ancestor genes. To understand better the mammalian chromosomal dispersion of this gene family and to facilitate studies of these genes in human illnesses and their animal models, we positioned the locus of each member in the rat, mouse, and human genomes. Our results indicate that each locus lies in a region of locally syntenic chromosomal homology across the three species.

Animals↗
PubMed1996

The rat genes encoding the pancreatitis-associated proteins I, II and III (Pap1, Pap2, Pap3), and the lithostathin/pancreatic stone protein/regeneration protein (Reg) colocalize at 4q33-->q34.

Using fluorescence in situ hybridization, we determined that the three rat PAP genes, and the related REG gene map in the same chromosomes region, namely 4q33-->q34. This rat chromosome region is thus homologous to the human 2p12 region, which also contains the PAP gene, the REG1A gene, and a REG-related gene (REGL).

Acute-Phase Proteins↗
PubMed1995

Identification of a novel conserved human gene, TEGT.

A novel gene, TEGT (testis enhanced gene transcript), has been identified in humans. It does not belong to any known gene family of vertebrates. The deduced amino acid sequence of the gene and a bacterial protein of unknown function show low but significant homology and very similar hydrophobicity profiles. Two different transcripts of TEGT occur, which are due to alternative usage of two polyadenylation sites. The presence of a nuclear targeting motif indicates that the gene product might localize to the nucleus. The TEGT gene maps to human chromosome 12q12-q13 and belongs to a syntenic group, which is conserved in human, mouse, and rat.

Animals↗
PubMed1995

Use of simple sequence length polymorphisms for genetic characterization of rat inbred strains.

Genetic monitoring is an essential component of colony management and for the rat has been accomplished primarily by using immunological and biochemical markers. Here, we report that simple sequence length polymorphisms (SSLPs) are a faster and more economical way of monitoring inbred strains of rats. We characterized 61 inbred strains of rats, using primer pairs for 37 SSLPs. Each of these loci appeared to be highly polymorphic, with the number of alleles per locus ranging between 3 and 14 and, as a result, all the 61 inbred strains tested in this study could be provided with a unique strain profile. These strain profiles are also used for estimating the degree of similarity between strains. This information may provide the rationale in selecting strains for genetic crosses or for other specific purposes.

Animals↗
PubMed1995

A genetic map of microsatellite markers on rat chromosome 7.

Nine microsatellite loci were mapped to rat Chromosome (Chr) 7 by genetic linkage and somatic cell hybrid analysis. These loci include the gene encoding a member of the IID sub-family of cytochrome P450 (Cyp2d), a gene with repetitive sequences expressed during myotube formation (D7Arb1e), four anonymous loci, D7Arb81, D7Arb208, D7Arb569, D7Arb609a, and three DNA loci defined by MapPair markers R245, R513, and R1071. The nine loci were all identified by PCR-based microsatellite polymorphism analysis and were characterized in 40 F2 intercross progeny of Fischer (F344/N) and Lewis (LEW/N) rats for segregation analysis. These markers formed a single linkage group spanning 76.8 cM with the following order and distances: D7Arb569-11.4 cM-D7Arb81-9.7 cM-R513-2.6 cM-Cyp2d-0.0 cM-R245-1.3 cM-D7Arb1e-10.4 cM-R1071-15.9 cM-D7Arb609a-15.4 cM-D7Arb208. Physical mapping of Cyp2d by somatic cell hybrid analysis allowed us to assign this linkage group to rat Chr 7. For each marker, two to six alleles were detected in a panel of 16 inbred rat strains (ACI/N, BN/SsN, BUF/N, DA/Bkl, F344/N, LER/N, LEW/N, LOU/MN, MNR/N, MR/N, SHR/N, SR/Jr, SS/Jr, WBB1/N, WBB2/N, WKY/N).

Alleles↗
PubMed1995

Mapping of the calcium-sensing receptor gene (CASR) to human chromosome 3q13.3-21 by fluorescence in situ hybridization, and localization to rat chromosome 11 and mouse chromosome 16.

The calcium-sensing receptor (CASR), a member of the G-protein coupled receptor family, is expressed in both parathyroid and kidney, and aids these organs in sensing extracellular calcium levels. Inactivating mutations in the CASR gene have been described in familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). Activating mutations in the CASR gene have been described in autosomal dominant hypoparathyroidism and familial hypocalcemia. The human CASR gene was mapped to Chromosome (Chr) 3q13.3-21 by fluorescence in situ hybridization (FISH). By somatic cell hybrid analysis, the gene was localized to human Chr 3 (hybridization to other chromosomes was not observed) and rat Chr 11. By interspecific backcross analysis, the Casr gene segregated with D16Mit4 on mouse Chr 16. These findings extend our knowledge of the synteny conservation of human Chr 3, rat Chr 11, and mouse Chr 16.

Animals↗
PubMed1995

The mammalian RPS6 gene, homolog of the Drosophila air8 tumor suppressor gene: is it an oncosuppressor gene?

The mammalian gene encoding the S6 ribosomal protein is the homolog of the Drosophila air8 tumor suppressor gene. We assigned the rat Rps6 gene to chromosome 5q22-33. The rat 5q22-33 chromosome region, previously shown to bear a malignant transformation suppressor gene, is homologous to the human 9p2l region, frequently deleted in various kinds of cancers and also containing at least one tumor suppressor (oncosuppressor) gene. To test the possibility that the Rps6 gene could be an oncosuppressor gene in mammals, we analysed its sequence and expression in normal and malignantly transformed cells. In mouse hepatoma cells (BWTG3), the Rps6 gene is hemizygously deleted but the remaining copy shows no sequence anomaly in the coding region, indicating that Rps6 is not oncosuppressor and that another gene acting as an oncosuppressor is located in its vicinity. In human tumor cells, the RPS6 gene is retained in cells showing deletion of the near-by gene, IFNB. Our results do not support the possibility that the RPS6 gene acts as an oncosuppressor gene in mammalian cells.

Animals↗
PubMed1995

Genetic map of eight microsatellite markers comprising two linkage groups on rat chromosome 6.

Five genes and three anonymous DNA loci were mapped to rat chromosome 6 by genetic linkage and somatic cell hybrid analyses. The eight loci were all identified by PCR-based microsatellite polymorphism analysis and were characterized in 40 F2 intercross progeny of Fischer (F344/N) and Lewis (LEW/N) inbred rats for segregation analysis. These markers formed two linkage groups spanning, respectively, 58.1 cM and 4.0 cM. The first linkage group is comprised of two anonymous DNA loci and four genes with the following map order and distances: D6Cep8 (previously D3)-17.9 cM-D6Arb309-2.5 cM-Vsnl1 (neural visinin-like protein)-20.4 cM-Prkar2b (type IIb regulatory subunit of cAMP-dependent protein kinase)-8.8 cM-Fkhl1 (forkhead-like transcription factor BF-1)-8.5 cM-Rnu1c (18-3A U1 RNA). The second linkage group is comprised of one gene, Ckb (creatine kinase, brain) and one anonymous DNA locus, D6Arb54, separated by 4.0 cM. For each marker, two to eight alleles were detected in a panel of 16 inbred rat strains (ACI/N, BN/SsN, BUF/N, DA/Bk1, F344/N, LER/N, LEW/N, LOU/MN, MNR/N, MR/N, SHR/N, SR/Jr, SS/Jr, WBB1/N, WBB2/N, and WKY/N). Comparative mapping information indicated that rat chromosome 6 exhibits syntenic conservation with mouse chromosome 12. Homologs of the rat chromosome 6 loci have been identified on human chromosomes 2, 7, and 14.

Animals↗
PubMed1995

Localization of the human HTF4 transcription factors 4 gene (TCF12) to chromosome 15q21.

Identification and localization of genes that encode regulators of transcription could provide landmarks for functional analysis of the human genome. Toward this goal, we examined a panel of somatic cell hybrids and assigned the gene (TCF12) encoding the helix-loop-helix transcription factors 4 (HTF4) to chromosome 15. Fluorescence in situ hybridization further localized TCF12 to chromosome 15q21. Northern analysis revealed that the relative abundance of HTF4 gene transcripts is not constant but varies depending on the human cell-line or tissue examined.

Animals↗
PubMed1995

The genes coding for rat cystatin-related prostate protein (Cstrp) map to chromosome 3q41.

Two genes encoding rat cystatin-related prostate protein (Cstrp), previously called CRP (Devos et al., 1993), were mapped to chromosome 3q41 by fluorescent in situ hybridization. The results were confirmed using a panel of mouse-rat hybrids that segregate rat chromosomes. Analysis of genomic DNA indicates that the Cstrp locus comprises probably more than three very similar genes.

Animals↗
PubMed1995

Chromosomal localization of the human and rat genes (PDE4D and PDE4B) encoding the cAMP-specific phosphodiesterases 3 and 4.

Through the use of somatic cell hybrids segregating either human or rat chromosomes, we determined the chromosome localizations of two genes encoding cAMP-specific phosphodiesterases (cAMP-PDEs). PDE4D, the gene encoding the cAMP-PDE isoform 3 (IVd), was assigned to human chromosome 5 and rat chromosome 2, and PDE4B, the gene encoding the cAMP-PDE isoform 4 (IVb), was assigned to human chromosome 1 and rat chromosome 5. These localizations extend the homology between rat chromosome 2 and human chromosome 5, on the one hand, and between rat chromosome 5 and human chromosome 1, on the other hand.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

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↗
PubMed1995

Mapping of quantitative trait loci for blood pressure and cardiac mass in the rat by genome scanning of recombinant inbred strains.

In the HXB and BXH recombinant inbred strains derived from the spontaneously hypertensive rat and the normotensive Brown Norway rat, we determined the strain distribution patterns of 500 genetic markers to scan the rodent genome for quantitative trait loci regulating cardiac mass and blood pressure. The markers spanned approximately 1,139 cM of the genome and were tested for correlations with left ventricular mass adjusted for body weight, and with systolic, diastolic, and mean arterial pressures. The marker for the dopamine 1A receptor (Drd1a) on chromosome 17 showed the strongest correlation with left ventricular heart weight (P = .00038, r = -0.59) and the relationship to heart weight was independent of blood pressure. The markers showing the strongest correlations with systolic, diastolic, and mean arterial pressure were D19Mit7 on chromosome 19 (P = .0012, r = .55), D2N35 on chromosome 2 (P = .0008, r = .56), and Il6 on chromosome 4 (P = .0018, r = .53), respectively. These studies demonstrate that the HXB and BXH strains can be effectively used for genome scanning studies of complex traits and have revealed several chromosome regions that may be involved in the genetic control of blood pressure and cardiac mass in the rat.

Animals↗
PubMed1994

The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat.

The chromosomal localization of the human and rat genes encoding the kainate-preferring glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5, respectively) was determined by Southern analysis of rat x mouse and human x mouse somatic cell hybrid panels and by fluorescence in situ hybridization. The localization of the mouse genes (Grik4 and Grik5) was established by interspecific backcross mapping. GRIK4 and GRIK5 are located on separate chromosomes (Chrs) in all species. GRIK4 mapped to human Chr 11q22.3, mouse Chr 9, and rat Chr 8. GRIK5 mapped to human Chr 19q13.2, mouse Chr 7, and rat Chr 1. The genes encoding the (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-preferring subunit GluR4, or GluRD (GRIA4), the neural cell adhesion molecule (NCAM), the D2 dopamine receptor (DRD2), and the Thy-1 cell surface antigen (THY1) have all been previously mapped to the human Chr 11q22 region. The mapping of the human GRIK4 and GRIK5 genes confirms and extends the relationship between human Chr 11 and mouse Chr 9 and also human Chr 19 and mouse Chr 7. GRIK4 is the fifth gene shared by human Chr 11 and rat Chr 8, whereas GRIK5 is 1 out of the 12 genes that are located on both human Chr 19 and rat Chr 1. Our data extend the conserved synteny established between certain human, mouse, and rat Chrs.

Animals↗
PubMed1994

Stable expression of human H1-histamine-receptor cDNA in Chinese hamster ovary cells. Pharmacological characterisation of the protein, tissue distribution of messenger RNA and chromosomal localisation of the gene.

A cDNA clone for the histamine H1 receptor was isolated from a human lung cDNA library; it encoded a protein of 487 amino acids which showed characteristic features of G-protein-coupled receptors. The percentages of identity of the deduced amino acid sequence with bovine, rat and guinea pig H1 histamine receptors were 82.6%, 79.4% and 73.3%, respectively, whereas these percentages decreased to 74.6%, 66% and 56.7% for the amino acid sequence of the third intracellular loop. The human H1-receptor cDNA was transfected into Chinese hamster ovary cells (CHO) via an eukaryotic expression vector; the receptor protein present on cell membranes specifically bound [3H]mepyramine with a Kd of 3.7 nM. The binding was displaced by H1-histamine-receptor antagonists and histamine. Northern blot analysis indicated the presence of two histamine H1 receptor mRNAs of 3.5 kb and 4.1 kb in various human tissues and an additional mRNA of 4.8 kb restricted to the human brain. Finally, by means of somatic cell hybrids segregating either human or rat chromosomes, the gene for histamine H1 receptor was found to reside on human chromosome 3 and rat chromosome 4.

Amino Acid Sequence↗
PubMed1994

Genetic identification of Mcs-1, a rat mammary carcinoma suppressor gene.

Women have inherited differences in their susceptibility to breast cancer, but the genes underlying this variation are difficult to identify. We have approached the problem of identifying breast cancer susceptibility genes by using a rat model. Inbred rat strains display differential susceptibilities to mammary carcinogenesis; the Copenhagen (COP) rat is resistant, while the Wistar-Furth (WF) rat is susceptible to induction of mammary tumors by 7,12-dimethylbenz[a]anthracene. Genetic breeding studies have shown that tumor resistance in the COP rat is a dominant phenotype, termed the rat mammary carcinoma suppressor trait. As a step toward defining the basis of this resistance, we undertook genetic mapping of this phenotype in a (WF x COP)F1 x WF backcross by studying a large collection of microsatellite and minisatellite polymorphisms. A total of 114 genetic markers, covering approximately 75% of the rat genome, were genotyped in the backcross progeny. A marker on rat chromosome 2 was found to show linkage to the resistance phenotype. Genetic linkage was demonstrated both in a qualitative analysis (in which rats were defined as resistant if they developed 0 tumors and sensitive if they developed two or more tumors; LOD score, 4.0) and in a quantitative trait locus analysis (in which tumor number was used as the quantitative phenotype; LOD score, 3.8). We infer the existence of a gene, Mcs-1, on rat chromosome 2 that suppresses mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗