Genetic modifiers that aggravate the neurological phenotype of the wobbler mouse.

The autosomal recessive mutation wobbler of the mouse (phenotype WR; genotype wr/wr) causes muscular atrophy due to motoneuron degeneration with 100% penetrance on the standard Mus musculus laboratorius C57BL/6J background. In inter- and backcrosses with M. m.

Homology between human chromosome 2p13.3 and the wobbler critical region on mouse chromosome 11: comparative high-resolution mapping of STS and EST loci on YAC/BAC contigs.

Human Chr 2p13-14 and homologous regions on mouse Chrs 6 and 11 have been subjects of previous studies because they comprise the loci for several neuromuscular diseases. Here we report on high-resolution mapping of 55 STS and EST loci on human Chr 2p13.3 and of 47 markers on the corresponding region on proximal mouse Chr.

The protein kinase N (PKN) gene PRKCL1/Prkcl1 maps to human chromosome 19p12-p13.1 and mouse chromosome 8 with close linkage to the myodystrophy (myd) mutation.

Protein kinase N (PKN) is a fatty acid- and Rho-activated serine/threonine protein kinase involved in the regulation of cell motility by association with cytoskeletal components such as neurofilament and alpha-actinin. We determined the chromosomal location of the human PKN gene PRKCL1 by fluorescence in situ hybridization and by radiation hybrid mapping. The corresponding mouse gene Prkcl1 was mapped by segregation analysis.

Integrated radiation hybrid map of human chromosome 2p13: possible involvement of dynactin in neuromuscular diseases.

The genes for the human neuromuscular diseases limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy are located on chromosome 2p13-p14, and two neuromuscular mutations of the mouse have been mapped to regions homologous to human chromosome 2p13 by conserved synteny, wobbler (wr) on proximal Chr 11 and motor neuron degeneration 2 (mnd2) on Chr 6. Neither one is a mouse homologue of LGMD2B. Recently the gene DCTN1, coding for the large subunit of the cytoskeletal protein dynactin, was shown by FISH to be located in this region and therefore should be considered a candidate for all these disease genes.

The human gene ZFP161 on 18p11.21-pter encodes a putative c-myc repressor and is homologous to murine Zfp161 (Chr 17) and Zfp161-rs1 (X Chr).

A clone from a lambda gt11 cDNA expression library of HeLa cells was isolated, sequenced, and shown to encode a new human zinc finger protein. The cDNA of the gene termed ZFP161 has an open reading frame of 1347 bp. The predicted protein comprises 449 amino acid residues and contains five zinc finger motifs of the Krüppel type near the C-terminus and a BTB/POZ domain in the N-terminal region.

Dynamin genes Dnm1 and Dnm2 are located on proximal mouse chromosomes 2 and 9, respectively.

Dynamins, microtubule-binding GTPases, are encoded by at least three genes in mammals. Two distinct gene-specific cDNAs were used to analyze the segregation of dynamin genes Dnm1 and Dnm2 in a mouse interspecies backcross. The nervous system-expressed gene Dnm1 was localized to Chr 2 between the genes for vimentin and nebulin, within a chromosomal region of conserved synteny to human chromosome 9q, consistent with the localization of the human dynamin-1 gene by FISH (see accompanying paper by Newman-Smith et al.

YAC contigs of the Rab1 and wobbler (wr) spinal muscular atrophy gene region on proximal mouse chromosome 11 and of the homologous region on human chromosome 2p.

Despite rapid progress in the physical characterization of murine and human genomes, little molecular information is available on certain regions, e.g., proximal mouse chromosome 11 (Chr 11) and human chromosome 2p (Chr 2p).

Chloride channel 2 gene (Clc2) maps to chromosome 16 of the mouse, extending a region of conserved synteny with human chromosome 3q.

The Clc2 gene of the mouse codes for the ubiquitously expressed chloride channel ClC-2, a member of a family of at least seven voltage gated chloride channels, some of which are implicated in hereditary diseases. Using a mouse interspecies back-cross panel, we have mapped Clc2 to Chr 16, proximal to the somatostatin gene Smst, extending a region of documented conserved synteny to human Chr 3q.

Interaction of plant profilin with mammalian actin.

The mode of interaction of birch and bovine profilins with actin was compared using a number of techniques. Birch profilin was purified from pollen or as a recombinant protein from Escherichia coli, using poly(L-proline) affinity chromatography and a monoclonal antibody for the identification of the isolated product. On two-dimensional gels, the genuine and recombinant proteins were identical in molecular mass and isoelectric point and revealed that birch profilin, in contrast to the basic profilins found in mammals, is an acidic protein, analogous to maize profilins.

Characterization of an F-actin-binding domain in the cytoskeletal protein vinculin.

Vinculin, a major structural component of vertebrate cell-cell and cell-matrix adherens junctions, has been found to interact with several other junctional components. In this report, we have identified and characterized a binding site for filamentous actin. These results included studies with gizzard vinculin, its proteolytic head and tail fragments, and recombinant proteins containing various gizzard vinculin sequences fused to the maltose binding protein (MBP) of Escherichia coli.