Biomedical subjects

U Deutsch

Publications and source records attributed to U Deutsch.

11 recordsLinked to original sources

PubMed1992

Pax1, a member of the paired box-containing class of developmental control genes, is mapped to human chromosome 20p11.2 by in situ hybridization (ISH and FISH).

Pax-1, a member of a murine multigene family, belongs to the paired box-containing class of developmental control genes first identified in Drosophila. The Pax-1 gene encodes a sequence-specific DNA-binding protein with transcriptional activating properties and has been found to be mutated in the autosomal recessive mutation undulated (un) on mouse chromosome 2 with vertebral anomalies along the entire rostrocaudal axis. By radioactive in situ hybridization (ISH) using a fragment from the murine Pax-1 paired box that is almost identical to the respective sequences from the cognate human gene HuP48 and fluorescence in situ hybridization (FISH) using a complete mouse Pax-1 cDNA, we have assigned the human homologue of murine Pax-1, the PAX1 locus, to chromosome 20p. The map position of PAX1 after FISH (FL-pter value of 0.34 +/- 0.04) corresponds to band p11.2. These results confirm the exceptional homology between human chromosome 20 and the distal segment of mouse chromosome 2, extending from bands F to G, and add PAX1 to the group of genes on 20p like PTPA, PRNP, SCG1, BMP2A, which are located in proximity on both chromosomes.

Animals↗

PubMed1991

The molecular basis of the undulated/Pax-1 mutation.

The murine paired box gene Pax-1 has been associated with the mouse developmental mutant undulated (un), which exhibits malformations in the vertebral column. In un mice, a point mutation leading to a Gly-Ser exchange in a conserved part of the paired domain of Pax-1 is present. Here we show that Pax-1 encodes a DNA-binding protein with transcriptional activating properties. The DNA-binding specificity of the Pax-1 protein has been extensively analyzed in gel shift assays, and in conjunction with binding interference experiments, a DNA-binding core motif was defined. Comparison of the DNA-binding properties of wild-type and un Pax-1 proteins demonstrates that the Gly-Ser replacement at position 15 within the paired domain dramatically decreases the DNA-binding affinity of the un Pax-1 protein and alters its DNA-binding specificity. These results decipher the molecular basis of the un mutation.

Alkylation↗

PubMed1991

Pax-3, a novel murine DNA binding protein expressed during early neurogenesis.

We describe the isolation and characterization of Pax-3, a novel murine paired box gene expressed exclusively during embryogenesis. Pax-3 encodes a 479 amino acid protein with an Mr of 56 kd containing both a paired domain and a paired-type homeodomain. The Pax-3 protein is a DNA binding protein that specifically recognizes the e5 sequence present upstream of the Drosophila even-skipped gene. Pax-3 transcripts are first detected in 8.5 day mouse embryos where they are restricted to the dorsal part of the neuroepithelium and to the adjacent segmented dermomyotome. During early neurogenesis, Pax-3 expression is limited to mitotic cells in the ventricular zone of the developing spinal cord and to distinct regions in the hindbrain, midbrain and diencephalon. In 10-12 day embryos, expression of Pax-3 is also seen in neural crest cells of the developing spinal ganglia, the craniofacial mesectoderm and in limb mesenchyme of 10 and 11 day embryos.

Amino Acid Sequence↗

PubMed1991

Pax: a murine multigene family of paired box-containing genes.

A murine multigene family has been identified that shares a conserved sequence motif, the paired box, with developmental control and tissue-specific genes of Drosophila. To date five murine paired box-containing genes (Pax genes) have been described and one, Pax-1, has been associated with the developmental mutant phenotype undulated. Here we describe the paired boxes of three novel Pax genes, Pax-4, Pax-5, and Pax-6. Comparison of the eight murine paired domains of the mouse, the five Drosophila paired domains, and the three human paired domains shows that they fall into six distinct classes: class I comprises Pox meso, Pax-1, and HuP48; class II paired, gooseberry-proximal, gooseberry-distal, Pax-3, Pax-7, HuP1, and HuP2; class III Pax-2, Pax-5, and Pax-8; class IV Pax-4; class V Pox neuro; and class VI Pax-6. Pax-1 and the human gene HuP48 have identical paired domains, as do Pax-3 and HuP2 as well as Pax-7 and HuP1, and are likely to represent homologous genes in mouse and man. Identical intron-exon structure and extensive sequence homology of their paired boxes suggest that several Pax genes represent paralogs. The chromosomal location of all novel Pax genes and of Pax-3 and Pax-7 has been determined and reveals that they are not clustered.

Amino Acid Sequence↗

PubMed1990

Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system.

The murine genome contains multiple genes with protein domains homologous to the Drosophila paired box, present in certain segmentation genes. At least one of these murine paired box (Pax) genes is associated with a developmental mutation. This report, in conjunction with the accompanying paper, describes a second member of this gene family, Pax2, that is also expressed during embryogenesis. Two overlapping cDNA clones were isolated and sequenced. At least two forms of the Pax2 protein can be deduced from the cDNA sequence. In addition to the highly conserved paired domain, an octapeptide sequence is located downstream. Expression of Pax2 is primarily restricted to the developing embryo in the excretory and central nervous systems. The transient nature of Pax2 expression during kidney organogenesis correlates with polarization and induction of epithelial structures and may indicate an important morphogenetic role for this gene.

Amino Acid Sequence↗

PubMed1990

Spatially and temporally restricted expression of Pax2 during murine neurogenesis.

The expression of the murine paired-box-containing gene, Pax2, is examined in the developing central nervous system by in situ hybridization. Pax2 expression is detected along the boundaries of primary divisions of the neural tube. Initially, Pax2 is expressed in the ventricular zone in two compartments of cells on either side of the sulcus limitans and along the entire rhombencephalon and spinal cord. At later times, Pax2 is restricted to progeny cells that have migrated to specific regions of the intermediate zone. In the eye, Pax2 expression is restricted to the ventral half of the optic cup and stalk and later to the optic disc and nerve. In the ear, expression is restricted to regions of the otic vesicle that form neuronal components. The transient and restricted nature of Pax2 expression suggests that this murine segmentation gene homologue may also establish compartmental boundaries and contribute to the specification of neuronal identity, as do certain Drosophila segmentation genes.

Animals↗

PubMed1988

undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax 1.

undulated (un) homozygous mice exhibit vertebral malformations along the entire rostro-caudal axis. Pax 1, a murine paired box-containing gene, is expressed in ventral sclerotome cells and later in intervertebral disks along the entire vertebral column. We localized the Pax 1 gene on chromosome 2 between beta 2-microglobulin and the agouti locus to an area where un maps. DNA analysis of the un mutant revealed a point mutation in a highly conserved part of the paired box of Pax 1, leading to a Gly-Ser replacement. The chromosomal location and the mutation in the paired box of un mice in conjunction with Pax 1 gene expression in wild-type mice implicate a causative role of Pax 1 in generation of the vertebral column.

Animals↗

PubMed1988

Moratorium call.

Explore the source record for details and available documents.

Base Sequence↗

PubMed1988

Pax 1, a member of a paired box homologous murine gene family, is expressed in segmented structures during development.

The mouse genome contains at least three copies of sequences homologous to the "paired box", a conserved domain in several Drosophila segmentation genes of the pair-rule and segment polarity classes. Overlapping phages were isolated from two different genomic libraries using the Drosophila gooseberry distal paired box as a probe. The hybridizing sequences are highly homologous to the conserved Drosophila paired box sequences. A single 3.1 kb Pax 1 (paired box gene) transcript was detected during embryonic development, whereas no transcripts were detected in adult tissues. Detailed in situ hybridization analyses with frozen embryonic sections demonstrated Pax 1 transcripts in the perichordal zone of the developing vertebral column. The expression pattern suggests a role for this gene in the formation of segmented structures of the mouse embryo.

Amino Acid Sequence↗

PubMed1988

The primary structure of the murine multifinger gene mKr2 and its specific expression in developing and adult neurons.

The complete amino acid sequence of the murine finger-containing gene mKr2 was determined. On the basis of sequence similarities in the repeated finger domain, mKr2 belongs to the same class of developmentally expressed genes as Drosophila Krüppel and hunchback. The presence of metal ion and DNA-binding finger domains similar to those identified in TFIIIA supports the hypothesis that these genes regulate transcription. mKr2 transcripts are restricted to neurons in the central and peripheral nervous system of adult animals. Furthermore, mKr2 transcripts can be detected in all the major structures of the developing nervous system during embryogenesis. The data are consistent with the hypothesis that mKr2 is a regulatory factor required for the differentiation and/or phenotypic maintenance of neurons.

Amino Acid Sequence↗

PubMed1987

A multigene family encoding several "finger" structures is present and differentially active in mammalian genomes.

Mouse genomic DNA contains multiple copies of sequences homologous to the Drosophila "Krüppel," a member of the "gap" class of developmental control genes of the fruit fly. The most interesting aspect of the homologous region is that, like Xenopus TFIIIA, it contains multiple finger-like folded domains capable of binding to nucleic acids. We have isolated six individual phages from a mouse genomic library on the basis of their DNA homology to Krüppel finger-coding probes, and describe here the DNA sequence and expression of two such clones containing finger-like structures. Upon differentiation of mouse teratocarcinoma cell line F9 with retinoic acid and cAMP, the expression of both genes was drastically reduced, and in one instance was undetectable. Each of the several other eukaryotic DNAs analyzed contained multiple copies of homologous genes with putative finger structures, indicating the presence of a finger-containing multigene family in higher organisms.

Amino Acid Sequence↗