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D R Beier

Publications and source records attributed to D R Beier.

At least 73 records · Page 4Linked to original sources
PubMed1995

Localization of a murine recessive polycystic kidney disease mutation and modifying loci that affect disease severity.

We have used a novel method of chromosomal exclusion to map the recessive mutation juvenile cystic kidney (jck) to mouse chromosome 11 using an intercross between (C57BL/6J x DBA/2J) F1jck/ + mice. The severity of polycystic kidney disease (PKD) in the intercross progeny was significantly more variable than that found in the parental C57BL/6J strain, suggesting that a modifier locus or loci introduced from DBA/2J affects expression of jck. Two regions--one from DBA/2J on chromosome 10 and a second from C57BL/6J on chromosome 1--are associated with inheritance of a more severe PKD phenotype. The finding of a highly significant association of inheritance of a C57BL/6J-related locus with disease severity, with a maximal QTL analysis lod score of 16.8, was unexpected; this result suggests that inheritance of both this locus and at least one DBA/2J locus results in the more severe phenotype, presumably as a consequence of a direct or indirect interaction between their protein products.

Animals↗
PubMed1995

A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis.

Mice that are homozygous for the autosomal recessive chondrodysplasia (cho) mutation die at birth with abnormalities in cartilage of limbs, ribs, mandible, and trachea. Limb bones of newborn cho/cho mice are wider at the metaphyses than normal bones and only about half the normal length. By linkage analysis, the cho gene and the gene encoding the alpha 1 (XI) chain of cartilage collagen XI were mapped to the same region of chromosome 3. Deletion of a cytidine residue about 570 nt downstream of the translation initiation codon in cho alpha 1 (XI) mRNA causes a reading frame shift and introduces a premature stop codon. The data demonstrate that collagen XI is essential for normal formation of cartilage collagen fibrils and the cohesive properties of cartilage. The results also suggest that the normal differentiation and spatial organization of growth plate chondrocytes is critially dependent on the presence of type XI collagen in cartilage extracellular matrix.

Amino Acid Sequence↗
PubMed1995

Haplotype analysis of intra-specific backcross curly-tail mice confirms the localization of ct to chromosome 4.

We have determined the order of a number of SSR and SSC polymorphic markers that map to distal mouse Chromosome (Chr) 4 and have used analysis of these markers in backcrosses designed to test the localization of the curly-tail (ct) mutation. We have confirmed that ct maps to this region, close to the locus D4Mit69. Our results also support the hypothesis that ct is a semidominant, rather than a recessive, mutation, since we have identified abnormal-tailed mice that are likely to be heterozygous at the ct locus. Finally, we examined Pax7 as a candidate gene for the ct mutation and found no evidence of protein sequence differences in ct compared with wild-type mice.

Alleles↗
PubMed1995

Quantitative locus analysis of airway hyperresponsiveness in A/J and C57BL/6J mice.

Airway hyperresponsiveness is a key characteristic of human asthma and a marker for asthma-like conditions in animals. F1 mice derived from A/J and C57BL/6J display a phenotype which resembles the asthma-like phenotype of the A/J mice. Since airway responsiveness failed to segregate as a mendelian trait, we show significant linkage at two loci, Bhr1 (lod = 3.0) and Bhr2 (lod = 3.7) on chromosomes 2 and 15. A third locus, Bhr3 (lod = 2.83), maps to chromosome 17. Each of these loci maps near candidate loci implicated in the pathobiology of asthma. Our study represents the first linkages established through a genome-wide survey of airway hyperresponsiveness in any mammal.

Analysis of Variance↗
PubMed1994

Molecular cloning and chromosome localization of a putative basolateral Na(+)-K(+)-2Cl- cotransporter from mouse inner medullary collecting duct (mIMCD-3) cells.

Electroneutral Na(+)-K(+)-2Cl- cotransporters represent one of the major routes for Cl- movement in epithelia. A secretory form of the cotransporter has been described in the basolateral membrane of a variety of epithelia from fish to mammals. We isolated a putative bumetanide-sensitive Na(+)-K(+)-2Cl- cotransporter cDNA, BSC2, from mIMCD-3 cells. Northern analysis indicates that in contrast to BSC1, the recently cloned renal-specific apical isoform of the cotransporter, BSC2 is expressed in secretory epithelia and thus appears to represent the basolateral isoform. Furthermore, BSC2 is also expressed in non-polarized cells, such as red cells and myocytes. Sequence comparison and chromosome localization demonstrate that BSC2 and BSC1 are different genes that diverged before the evolution of vertebrates.

Amino Acid Sequence↗
PubMed1994

The genes encoding alpha 2(IX) collagen (COL9A2) map to human chromosome 1p32.3-p33 and mouse chromosome 4.

We have determined the chromosomal locations of the human and murine genes coding for alpha 2(IX) collagen, a polypeptide subunit of the heterotrimeric type IX collagen molecule. COL9A2 was mapped to human chromosome 1p32.3-p33 using fluorescence in situ hybridization. A single-strand conformational polymorphism within the murine Col9a2 gene was used to map this locus to mouse chromosome 4. We also present new sequence data, which completes the coding information for the human alpha 2(IX) chain and revises the sequence for the chicken alpha 2(IX) chain. This permits comparison of the carboxyl-terminal (NC1) domains of the alpha 1(IX), alpha 2(IX), and alpha 3(IX) chains across several species.

Amino Acid Sequence↗
PubMed1994

A genetic analysis of neocortical ectopias in New Zealand black autoimmune mice.

Two experiments investigated the heritability of neocortical ectopias seen in 30-40% of New Zealand Black (NZB/BINJ) autoimmune mice. The first study examined the brains of mice from the NZB x SM/J recombinant inbred (RI) strains. Fifteen RI inbred strains were examined and over half had ectopias suggesting that a major gene was involved in ectopia production. A follow-up experiment comparing the incidence of ectopias among crosses between NZB and control DBA/2 strains showed that the predisposition to develop ectopias in NZB is a recessively inherited trait with incomplete penetrance.

Animals↗
PubMed1994

Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13.1-q21.1 and mouse chromosome 5.

The gonadotropin-releasing hormone receptor (GRHR) is a G-protein-coupled receptor on the cell surface of pituitary gonadotropes, where it serves to transduce signals from the extracellular ligand, the hypothalamic factor gonadotropin-releasing hormone, and to modulate the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. We have localized the GRHR gene to the q13.1-q21.1 region of the human chromosome 4 using mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4. Furthermore, using linkage analysis of single-strand conformational polymorphisms, the murine GRHR gene was localized to mouse chromosome 5, linked to the endogenous retroviral marker Pmv-11. This is consistent with te evolutionary conservation of homology between these two regions, as has been previously suggested from comparative mapping of several other loci. The localization of the GRHR gene may be useful in the study of disorders of reproduction.

Animals↗
PubMed1994

CD19 maps to a region of conservation between human chromosome 16 and mouse chromosome 7.

CD19 is a B lymphocyte cell surface protein expressed from the earliest stages of B lymphocyte development until their terminal differentiation into plasma cells. In this report the human CD19 gene (hCD19) was localized to band p11.2 on the proximal short arm of chromosome 16 by in situ hybridization to metaphase chromosomes, using hCD19 cDNA as probe. hCD19 gene localization was confirmed by polymerase chain reaction based analysis with hCD19-specific primers, using a panel of human/hamster somatic cell hybrid DNA as templates. The mouse CD19 gene (mCd19) was mapped to bands F3-F4 of chromosome 7 by in situ hybridization to metaphase chromosomes, using a mCD19 cDNA probe. Segregation analysis of nucleotide sequence polymorphisms in interspecific backcross progeny revealed linkage of mCd19 with hemoglobin beta (Hbb), Int-2, and H19, other loci previously mapped to the same region of mouse chromosome 7, confirming the localization of mCd19 to this region. The order of these loci was determined to be centromere--Hbb--mCd19--H19--Int-2--telomere. The genetic distances between the loci examined, calculated from the recombination frequencies, suggested that mCd19 was located centrally between Hbb and H19. This region of mouse chromosome 7 is homologous to the region of human chromosome 16 to which the hCD19 gene maps. Multiple genes with a lymphocyte-related function also map to this conserved region including genes encoding the IL-4 receptor, CD11a, CD11b, CD11c, CD43 (leukosialin), and protein kinase C beta polypeptide.

Animals↗
PubMed1994

Isolation of a receptor tyrosine kinase (DTK) from embryonic stem cells: structure, genetic mapping and analysis of expression.

Analysis of receptor tyrosine kinases expressed during mouse embryonic stem cell differentiation resulted in the cloning of a receptor designated developmental tyrosine kinase (DTK). The 850 amino acid mature receptor protein comprises an extracellular domain with two immunoglobulin-like motifs and two fibronectin type III modules, a 25 amino acid transmembrane domain and a cytoplasmic region with a catalytic kinase domain. In embryonic stem cells growing in the presence of leukemia inhibitory factor DTK is abundantly expressed and this level of expression is maintained in differentiating embryonic stem cells and cystic embryoid bodies. In mid-gestational embryos (E14.5), DTK RNA is expressed in many tissues including brain, eye, thymus, lung, heart, gut, liver, testis and limbs. In contrast, expression of DTK in adult mice becomes restricted to brain, portions of the gastrointestinal tract, bladder, testis and ovary. There is enrichment of transcripts encoding DTK in purified fetal liver hematopoietic stem cells, when compared with unfractionated fetal liver. The DTK gene maps to mouse chromosome 2, band F.

Amino Acid Sequence↗
PubMed1993

Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene.

Mice homozygous for the recessive allelic mutation motheaten (me) or viable motheaten (mev) on chromosome 6 develop severe defects in hematopoiesis. In this paper we present the findings that the me and mev mutations are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. High resolution mapping localized me to an area tightly linked to Hcph on chromosome 6. Abnormalities of the Hcph protein product were demonstrated by Western blot analysis and by activity assays in both me/me and mev/mev mice. Molecular analysis of the Hcph cDNA identified abnormal transcripts in both mutants. DNA sequence analyses of cDNA and genomic clones revealed that both the me and mev mutations are point mutations that result in aberrant splicing of the Hcph transcript. These findings provide the first available animal models for a specific protein-tyrosine phosphatase deficiency, thus facilitating determination of the precise role of this signaling molecule in hematopoiesis.

Animals↗
PubMed1993

Mapping the midkine family of developmentally regulated signaling molecules.

Midkine (Mdk) and heparin-binding neurotrophic factor (Hbnf)/pleiotrophin (Ptn) comprise the Midkine family of developmentally regulated signaling molecules. We have determined the chromosomal localization of these genes in the mouse by use of single-strand conformation polymorphisms (SSCPs), which facilitated the typing of Mdk and Hbnf alleles in recombinant inbred (RI) strains and interspecific backcrosses. Mapping was performed relative to other cloned genes, as well as simple sequence length polymorphisms (SSLPs) in the interspecific backcrosses. Mdk maps to mouse Chromosome (Chr) 2, linked to the Hoxd gene cluster. Hbnf maps to proximal mouse Chr 6, linked to the Cftr and Cpa genes. Comparative mapping of human MDK and HBNF employing species-specific polymerase chain reaction (PCR) primers and human monochromosomal somatic cell hybrids assigns MDK to human Chr 11 and HBNF to human Chr 7q32-qter.

Animals↗
PubMed1993

Juvenile cystic kidneys (jck): a new mouse mutation which causes polycystic kidneys.

We have characterized a new recessive mutation in the mouse which predisposes to the development of polycystic kidney disease. This mutation, called juvenile cystic kidneys (jck), arose in a transgenic line of mice, but appears unrelated to the transgene since it segregates freely from it. While focal cysts are evident in affected animals as early as three days of life and the disease is progressive, the mice are fertile and generally survive to four or more months of age. Complementation analysis indicates that the jck mutation is not allelic with three other known recessive polycystic kidney mutations (cpk and two as yet unnamed mutations), and linkage studies demonstrate it is unlikely to be allelic with a fourth (pcy). The study of these five mutations and their interactions should prove useful for understanding the mechanisms required to maintain the normal integrity of renal tubules.

Alleles↗
PubMed1992

Mapping genes in the mouse using single-strand conformation polymorphism analysis of recombinant inbred strains and interspecific crosses.

We have utilized a PCR-based analysis of single-strand conformation polymorphisms to identify polymorphisms that can be used for mapping cloned DNA sequences in the mouse. We have found that single-strand conformation polymorphism analysis of sequences that are potentially less subject to conservation (i.e., intron and 3' untranslated regions) is a relatively efficient means of detecting polymorphisms between inbred strains. Fifty percent of the tested primer pairs were polymorphic between inbred strains and 90% were polymorphic between mouse species, which is a frequency comparable to that found for microsatellite repeat sequences. We have found that this technique can be readily used to determine the strain distribution pattern in a recombinant inbred series and is a simple and rapid means to obtain a map position for cloned sequences. When this strategy was tested on a number of previously mapped cloned genes, the strain distribution patterns obtained were consistent with that to be expected on the basis of the known map position. We also tested the utility of this approach for characterizing genes that have not been previously mapped. Dvl, the mouse homolog of the putative Drosophila dishevelled gene, and Adfp, encoding an adipocyte differentiation-related protein, were found to map to chromosome 4. These results were confirmed using single-strand conformation polymorphism analysis of an interspecific backcross.

Animals↗
PubMed1991

Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis.

Genomic imprinting is a regulatory process that requires a cell to recognize the parental origin of alleles. To understand how these alleles are distinguished, we have assessed changes in the DNA methylation of an imprinted transgene as it switches from one inheritance pattern to another while moving through gametogenesis and embryogenesis. We find that both maternally and paternally inherited methylation patterns are erased in primordial germ cells and that distinctive patterns emerge during germ cell maturation. In the case of the maternal allele, the methylation pattern is fully acquired during oogenesis. In the case of the paternal allele, the methylation pattern found in sperm undergoes further modification during embryogenesis. Thus, the distinction between "erased" maternal and paternal alleles is first established during their residence in different germ cells and then may be maintained by the recognition of the distinctive patterns that each allele displays in the zygote.

Alleles↗
PubMed1991

Close linkage of a transgene insertion site to the steel (Sl) locus on mouse chromosome 10.

The characterization of the insertion sites of exogenous sequences in transgenic mice can identify loci that are potentially useful for the genetic analysis of the mammalian genome. We have found that the transgene insertion site in the transgenic line TG.EB is tightly linked with the Steel (Sl) locus on mouse chromosome 10. In a backcross between doubly heterozygous transgenic Sl (Tg.EB +/+ Sl) mice and wild-type mice, only one recombinant was found in 135 progeny (recombination percentage = 0.7 +/- 0.7). The recombination frequency of the transgene with marker loci known to flank Sl was consistent with a map position close to Sl. Genomic sequences that are adjacent to the transgene insertion site were cloned and found to be tightly linked with the Sl locus in interspecific crosses using nontransgenic mice. Recombination analysis utilizing the transgene insertion site locus was used to show that a recently identified hematopoietic growth factor is encoded at Sl. The cloned sequences from the transgene insertion site are polymorphic in inbred strains of mice and can be utilized to determine the genotype at Sl during early embryonic development. Further, they may be useful in characterizing the genomic region near Sl that is affected in Sl deletion mutants.

Animals↗
PubMed1990

The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus.

Mutations at the steel locus (Sl) of the mouse affect the same cellular targets as mutations at the white spotting locus (W), which is allelic with the c-kit proto-oncogene. We show that KL, a hematopoietic growth factor obtained from conditioned medium of BALB/c 3T3 fibroblasts that stimulates the proliferation of mast cells and early erythroid progenitors, specifically binds to the c-kit receptor. The predicted amino acid sequence of isolated KL-specific cDNA clones suggests that KL is synthesized as an integral transmembrane protein. Linkage analysis maps the KL gene to the Sl locus on mouse chromosome 10, and KL sequences are deleted in the genome of the Sl mouse. These results indicate that the Sl locus encodes the ligand of the c-kit receptor, KL.

Amino Acid Sequence↗