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M S Buckwalter

Publications and source records attributed to M S Buckwalter.

11 recordsLinked to original sources
PubMed1997

Construction of a 3-Mb contig and partial transcript map of the central region of mouse chromosome 11.

We report the establishment of a high-resolution genetic map, a physical map, and a partial transcript map of the Ames dwarf critical region on mouse chromosome 11. A contig of 24 YACs and 13 P1 clones has been assembled and spans approximately 3 Mb from Flt4 to Tcf7. A library of approximately 1000 putative transcript clones from the region was prepared using exon amplification and pituitary cDNA selection. Ten novel transcripts were partially characterized, including a member of the olfactory receptor family, an alpha-tubulin-related sequence, and a novel member of the cdc2/CDC28-like kinase family, Clk4. The location of Prop1, the gene responsible for Ames dwarfism, has been localized within the contig. This contig spans a region of mouse chromosome 11 that exhibits linkage conservation with human chromosome 5q23-q35. The strength of the genetic map and genomic resources for this region suggest that comparative DNA sequencing of this region could reveal the genes responsible for other mouse mutants and human genetic diseases.

Animals↗
PubMed1997

Genetic mapping of 21 genes on mouse chromosome 11 reveals disruptions in linkage conservation with human chromosome 5.

We report a high-resolution genetic map of 21 genes on the central region of mouse Chr 11. These genes were mapped by segregation analysis of more than 1650 meioses from three interspecific backcrosses. The order of these genes in mouse was compared to the previously established gene order in human. Eighteen of the 21 genes map to human Chr 5, and 2 of the genes define a proximal border for the region of homology between mouse Chr 11 and human Chr 17. Our results indicate a minimum of four rearrangements within the 10-cM region of synteny homology between mouse Chr 11 and human Chr 5. In addition, the linkage conservation is disrupted by groups of genes that map to mouse Chrs 13 and 18. These data demonstrate that large regions of conserved linkage can contain numerous chromosomal microrearrangements that have occurred since the divergence of mouse and human ancestors. Comparison of the mouse and human maps with data for other species provides an emerging picture of mammalian chromosome evolution.

Animals↗
PubMed1994

A missense mutation in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor in the spasmodic mouse.

Hereditary hyperekplexia, an autosomal dominant neurologic disorder characterized by an exaggerated startle reflex and neonatal hypertonia, can be caused by mutations in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor (GLRA1). Spasmodic (spd), a recessive neurologic mouse mutant, resembles hyperekplexia phenotypically, and the two disease loci map to homologous chromosomal regions. Here we describe a Glra1 missense mutation in spd that results in reduced agonist sensitivity in glycine receptors expressed in vitro. We conclude that spd is a murine homologue of hyperekplexia and that mutations in GLRA1/Glra1 can produce syndromes with different inheritance patterns.

Amino Acid Sequence↗
PubMed1994

A frameshift mutation in the mouse alpha 1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death.

The neurologic mutant mouse, oscillator, is characterized by a fine motor tremor and muscle spasms that begin at 2 weeks of age and progressively worsen, resulting in death by 3 weeks of age. We report the localization of the oscillator mutation to the central region of mouse Chr 11, and demonstrate its allelism with spasmodic, a recessive viable neurological mutation which displays excessive startle. Oscillator is caused by a microdeletion in the gene coding for the alpha 1 subunit of the adult glycine receptor (Glra1). Glra1 assembles into a pentameric complex with the beta subunit of the glycine receptor (3 alpha (1)2 beta 5) to form a glycine-gated chloride channel. This receptor is the major adult glycine receptor, and the site of action of the poison strychnine. The oscillator deletion causes a frameshift resulting in loss of the highly conserved third cytoplasmic loop and fourth transmembrane domain of the protein. Membranes isolated from oscillator homozygote spinal cords display a 90% reduction in glycine-displaceable strychnine binding. This lack of ligand binding function confirms that oscillator is a complete loss of function allele. The oscillator mutation provides evidence that although at least four different alpha subunits exist for the glycine receptor, none of the other subunits can compensate for the loss of alpha 1 function. Mutations which impair GLRA1 function in humans have been shown to cause dominant familial startle disease. The identification of the oscillator mutation suggests that severe loss of function alleles in humans would result in prenatal or neonatal lethality.

Amino Acid Sequence↗
PubMed1993

Genetic mapping and evaluation of candidate genes for spasmodic, a neurological mouse mutation with abnormal startle response.

Spasmodic (spd) is a recessive mouse mutation characterized by a prolonged righting reflex, fine motor tremor, leg clasping, and stiffness. Using an intersubspecific backcross that segregates spd, we placed spd on Chr 11 with the following gene order: Adra-1-3.8 +/- 2.1 cM-Pad-1-6.3 +/- 2.7-(spd, Anx-6, Csfgm, Glr-1, Il-3, Il-4, Il-5, Sparc)-9.1 +/- 2.4-D11 Mit5-2.2 +/- 1.5-Asgr-1. This localization eliminated the alpha 1-adrenergic receptor (Adra-1) and the alpha 1 and gamma 2 subunits of the GABAA receptor as candidate genes. Two other promising candidate genes, annexin VI (Anx-6) and a glutamate receptor (Glr-1), were mapped to within 2.1 cM of the spd locus. Although no recombination was observed between spd and Anx-6 or Glr-1, no evidence was obtained for a lesion in either gene. The presence of normal Anx-6 and Glr-1 mRNA transcripts was confirmed by Northern blot analysis, in situ hybridization, and DNA sequence analysis. The localization of Anx-6 and Glr-1 extends the known synteny homology between human chromosome 5q21-q31 and mouse Chr 11 and reveals the probable chromosomal location of the human counterpart to spd. Synteny homology and phenotypic similarities suggest that spasmodic mice may be a genetic model for the inherited human startle disease, hyperekplexia (STHE).

Alternative Splicing↗
PubMed1991

Localization of the panhypopituitary dwarf mutation (df) on mouse chromosome 11 in an intersubspecific backcross.

Ames dwarf (df) is an autosomal recessive mutation characterized by severe dwarfism and infertility. This mutation provides a mouse model for panhypopituitarism. The dwarf phenotype results from failure in the differentiation of the cells which produce growth hormone, prolactin, and thyroid stimulating hormone. Using the backcross (DF/B-df/df X CASA/Rk) X DF/B-df/df, we confirmed the assignment of df to mouse chromosome 11 and demonstrated recombination between df and the growth hormone gene. This backcross is an invaluable resource for screening candidate genes for the df mutation. The df locus maps to less than 1 cM distal to Pad-1 (0.85 +/- 0.85 cM). Two new genes localized on mouse chromosome 11, Rpo2-1, and Edp-1, map to a region of conserved synteny with human chromosome 17. The localization of the alpha 1 adrenergic receptor, Adra-1, extends a known region of synteny conservation between mouse chromosome 11 and human chromosome 5, and suggests that a human counterpart to df would map to human chromosome 5.

Animals↗
PubMed1988

Bacteriophage Mu sites required for transposition immunity.

Plasmids with bacteriophage Mu sequences receive additional Mu insertions 20-700 times less frequently than plasmids without Mu sequences. The Mu sites required for this transposition immunity were mapped near each end, either of which was sufficient. The left site was between 127 and 203 base pairs from the left end, and the right site was between 22 and 93 base pairs from the right end. These sequences include the innermost but not the outermost of the three binding sites for the Mu A transposition protein at each end of Mu. Transposition immunity was cis-acting and independent of its location on a target plasmid. An additional copy of an immunity site reduced transposition a factor of 10 further. Transposition immunity was seen both during full phage lytic growth, with all the bacteriophage Mu genes, and during normal cellular growth, with a mini-Mu element containing only the Mu c and ner regulatory and A and B transposition genes.

Bacteriophages↗