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Biomedical subjects

F H Ruddle

Publications and source records attributed to F H Ruddle.

At least 19 recordsLinked to original sources
PubMed1992

Expression pattern of a murine homeobox gene, Dbx, displays extreme spatial restriction in embryonic forebrain and spinal cord.

Homeobox genes specify regional identity during development. A homeobox sequence that we have named Dbx was isolated from 13.5-day embryonic mouse telencephalon cDNA. The Dbx homeodomain shows highest sequence homology to Drosophila H2.0 and chicken CHox E. We report here the expression pattern of Dbx during mouse embryogenesis. In situ hybridization analyses indicate that Dbx is expressed exclusively within the embryonic central nervous system in a highly restricted manner. Dbx transcripts are detected within a region of the prospective cerebral cortex of the midgestation telencephalon. Dbx is also expressed in the diencephalon as well as in two thin continuous columns of neuroblasts within the hindbrain and spinal cord. This expression is limited to regions of active mitosis. Dbx may act to specify subsets of neuroblasts during the development of the central nervous system.

Amino Acid Sequence↗
PubMed1992

Genetic linkage analysis of the murine developmental mutant velvet coat (Ve) and the distal chromosome 15 developmental genes Hox-3.1, Rar-g, Wnt-1, and Krt-2.

We have identified restriction fragment length polymorphisms between Mus musculus and Mus spretus for the Chromosome 15 loci Hox-3, Wnt-1, Krt-2, Rar-g, and Ly-6. We followed the inheritance of these alleles in interspecific genetic test crosses between velvet coat (Ve) heterozygotes and M. spretus. The results suggest a gene order and recombination distances (in cM) of Ly-6-22-Wnt-1-2-Ve/Krt-2/Rar-g-3-Hox-3. No recombination was found between Ve, Krt-2, and Rar-g. The data also provide evidence for the hypothesis of a large-scale genomic duplication involving homologous gene pairs on mouse Chromosomes 15 and 11.

Animals↗
PubMed1992

Chromosome assignments of the human TNF p55 and p75 receptor genes.

At least two different receptor molecules have been described that are capable of binding tumor necrosis factor alpha, a cytokine that plays an important role in inflammation and antitumor activity. Comparative analyses at the nucleotide sequence level suggest that these receptors are members of a newly defined protein family that also includes human and rat nerve growth factor receptors. In this study, we determine the chromosome assignments of the human TNF alpha receptor genes, one of which may have evolved as part of a conserved Hox locus-containing chromosome segment.

Base Sequence↗
PubMed1992

Repression of the beta-amyloid gene in a Hox-3.1-producing cell line.

Mammalian homeobox genes are widely expressed in the developing central nervous system and are postulated to control developmental processes by regulating gene expression at the transcriptional level. In vitro studies have identified consensus DNA sequences that contain an ATTA core as sites for interaction with homeodomain proteins. Such elements have been found in the upstream regulatory region of the gene encoding beta-amyloid precursor protein, which is associated with the neurological disorder Alzheimer disease. As the beta-amyloid precursor protein gene is also expressed in the developing central nervous system and appears to play a role in cellular regulatory processes, we have examined the possibility that a homeobox gene product can regulate its transcription. We demonstrate by Northern blot analyses and transfection experiments that the expression of the beta-amyloid precursor protein gene is decreased in cultured cells expressing the mouse homeobox gene Hox-3.1.

Amyloid beta-Protein Precursor↗
PubMed1992

Genetic mapping of a new homeobox gene to mouse chromosome 7.

A newly identified homeobox gene designated Dbx has been mapped to mouse Chromosome (Chr) 7. This gene is expressed in a restricted manner in developing mouse brain and spinal cord and has amino acid sequence similarities with members of the homeobox gene family such as Drosophila H2.0 and mouse Hlx. Using a fragment of the Dbx cDNA as a probe, a PstI restriction fragment length polymorphism was used to determine genotypes of 144 progeny from an interspecific backcross. Segregation analysis revealed linkage of Dbx with six prepositioned reference loci on mouse Chr 7. No recombination was observed between Dbx and Odc-rs6, indicating that Dbx lies approximately 25 cM distal to the Chr 7 centromere in a region that has conserved linkage relationships with regions of human Chrs 11 and 19.

Animals↗
PubMed1991

Detection of homeobox genes in development and evolution.

The homeobox genes encode a family of DNA-binding regulatory proteins whose function and genomic organization make them an important model system for the study of development and differentiation. Oligonucleotide primers corresponding to highly conserved regions of Antennapediaclass homeodomains were designed to detect and identify homeobox sequences in populations of DNA or RNA by means of the polymerase chain reaction (PCR). Here we present a survey of sequences detected by PCR using an initial set of primers (HoxA and HoxB) based on an early nucleotide consensus for vertebrate Antennapedia-class homeodomains. Several novel sequences are reported from both mouse genomic DNA and RNA from the developing mouse telencephalon. Forebrain-derived clones are similar to the chicken CHox7, Drosophila H2.0, and mouse Hlx genes. PCR also proved to be a rapid method for identifying homeobox sequences from diverse metazoan species. Cloning of three Antennapedia-related sequences from cnidarians provides evidence of ancient roles for homeobox genes early in metazoan evolution.

Amino Acid Sequence↗
PubMed1991

Partial purification of Xenopus laevis egg extract factor(s) that induce swelling in permeabilized human sperm.

A combination of adsorption (protamine-agarose) and gel filtration (Sephacryl S-300) chromatography was used to enrich for factor(s) in Xenopus laevis frog egg extract that induce nuclear swelling-chromatin decondensation in permeabilized human sperm. It was determined that a 70-fold purification of the factor(s) that induce human sperm nuclear swelling has resulted from the purification scheme. The reduced, active factor(s) have a Kav of 0.12 and an approximate molecular weight of 290,000 daltons. The extract nuclear swelling activity is sensitive to temperatures of 50 degrees C and above, as well as proteolytic treatment. RNase and cycloheximide treatments of the extracts have no effect on the nuclear swelling activity. These data suggest that the egg extract factor(s) that induce nuclear swelling in permeabilized human sperm are protein(s) that are present in the unfertilized frog egg.

Animals↗
PubMed1991

Homeoboxes in cnidarians.

Homeoboxes have previously been documented from various phyla of triploblastic, coelomate and pseudocoelomate, animals. We report here the first homeoboxes from cnidarians, a phylum of diploblastic organisms thought to occupy a near-basal position in metazoan phylogeny. We have sequenced three partial (77 bp) fragments of Antennapedia (Antp) class homeoboxes from the hydroids Hydractinia symbiolongicarpus and Eleutheria dichotoma. A pair of fragments, Cnox-2-Hs and Cnox-2-Ed, from the two species differ in nucleotide sequences but have identical derived amino acid sequences. A gene tree produced by parsimony analysis shows that these two fragments cluster within the Antp homeobox lineage. The third fragment, Cnox-1, clusters as a sister group of the other Antp class homeoboxes.

Amino Acid Sequence↗
PubMed1991

Glial fibrillary acid protein, an astrocytic-specific marker, maps to human chromosome 17.

The murine glial fibrillary acid protein (GFAP) gene is located on chromosome 11 in close proximity to the genes encoding transforming protein p53 (Trp53) and myeloperoxidase (Mpo). Both Trp53 and Mpo have been mapped to human chromosome 17, but the chromosomal assignment of human GFAP has not been previously determined. In this report, we have amplified a cDNA fragment encoding a portion of GFAP from human brain and have used this probe to screen a mouse x human somatic cell hybrid panel. The results show that a human-specific GFAP species of approx 3.7 kb maps to one of these lines, TMS5, which contains chromosome 17 as its only human chromosome. On the basis of these data we speculate that there may be evolutionary relatedness between GFAP and other genes that map to both murine chromosome 11 and human chromosome 17.

Animals↗
PubMed1991

The peripherin gene maps to mouse chromosome 15.

We have mapped the mouse peripherin gene, Prph, to chromosome 15 by means of Southern analysis of a panel of Chinese hamster/mouse somatic cell hybrids using a rat peripherin cDNA probe. Peripherin is a recently characterized type III intermediate filament expressed in the peripheral and the central nervous system. Although its exact function is not known, peripherin is likely to be involved in the neuronal cytoskeleton, a role it shares with other intermediate filaments, such as the neurofilament proteins. The intermediate filament gene family is believed to have evolved via gene duplication and dispersal throughout the genome; these processes have resulted in clusters of intermediate filament genes on specific chromosomes and conservation of these chromosomal locations among mammalian species.

Animals↗
PubMed1991

Timing of paternal Pgk-1 expression in embryos of transgenic mice.

In mouse development, the paternal allele of the X-linked gene Pgk-1 initiates expression on day 6, two days later than the maternal allele, which is activated on day 4. The different timing of expression of the maternal and paternal alleles may be determined by (i) imprinting of the chromosome region in which the gene resides, but not aimed specifically at the Pgk-1 gene; (ii) gene specific imprinting, acting on Pgk-1 irrespective of the chromosomal localization of the gene; (iii) an interplay between embryo cell differentiation, timing of X-inactivation and Pgk-1 expression, without the involvement of imprinting at the Pgk-1 locus itself (Fundele R., Illmensee, K., Jagerbauer, E. M., Fehlau, M. and Krietsch, W. K. (1987) Differentiation 35, 31-36). Our findings in transgenic mouse lines, carrying Pgk-1 on autosomes, indicate the importance of the X chromosomal location for the delayed expression of the paternal Pgk-1 allele, and are in agreement with the first of the explanations listed above. We propose that the late activation of the paternal Pgk-1 locus is a consequence of imprinting targeted at, and centered around, the X chromosome controlling element.

Animals↗
PubMed1991

A regulatory region from the mouse Hox-2.2 promoter directs gene expression into developing limbs.

To characterize cis-acting regulatory elements of the murine homeobox gene, Hox-2.2, transgenic mouse lines were generated that contained the LacZ reporter gene under the control of different fragments from the presumptive Hox-2.2 promoter. A promoter region of 3600 base pairs (bp) was identified, which reproducibly directed reporter gene expression into specific regions of developing mouse embryos. At 8.5 days postcoitum (p.c.) reporter gene activity was detected in posterior regions of the lateral mesoderm and, in subsequent developmental stages, expression of the LacZ gene was restricted to specific regions of the developing limb buds and the mesenchyme of the ventrolateral body region. This pattern of Hox-2.2-LacZ expression was found in all transgenic embryos that have been generated with the 3.6 kb promoter fragment (two founder embryos and embryos from five transgenic lines). In addition, embryos from two transgenic mouse lines expressed the reporter gene at low levels in the developing central nervous system (CNS). Our results are consistent with the idea that in addition to their presumptive role in CNS and vertebrae development, Hox-2.2 gene products are involved in controlling pattern formation in developing limbs.

Animals↗
PubMed1991

Homeobox genes in mouse development.

Following the discovery of the homeobox as a conserved sequence in developmentally important genes of Drosophila, a plethora of such sequences have been identified in evolutionarily distant organisms. Among mammals, the mouse homeobox genes have been studied most intensively with a hope of deciphering basic mechanisms of embryonic development. The genomic arrangement of many mouse homeobox genes is similar to the organization of the Drosophila genes, suggesting that they arose as a consequence of gene duplication and divergence from a primordial cluster during evolution. Homeobox genes encode proteins that may form a part of the autoregulatory and transregulatory network specifying positional value in the embryo. Supporting this view, the more diverged members of this growing family function as transcription factors, some of which regulate the expression of tissue-specific genes. Mouse homeobox genes are expressed during embryonic development in a spatially restricted manner and alterations in their expression pattern can disrupt embryonic development. The implications of these findings will be discussed in the context of the role of homeobox genes in the embryonic development of Drosophila and other organisms.

Amino Acid Sequence↗