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C S Montgomery

Publications and source records attributed to C S Montgomery.

11 recordsLinked to original sources
PubMed1995

Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse.

The homozygous and heterozygous phenotypes are described and characterized for 45 new pink-eyed dilution (p) locus mutations, most of them radiation-induced, that affect survival at various stages of mouse development. Cytogenetically detectable aberrations were found in three of the new p mutations (large deletion, inversion, translocation), with band 7C involved in each case. The complementation map developed from the study of 810 types of compound heterozygotes identifies five functional units: jls and jlm (two distinct juvenile-fitness functions, the latter associated with neuromuscular defects), pl-1 and pl-2 (associated with early-postimplantation and preimplantation death, respectively), and nl [neonatal lethality associated with cleft palate (the frequency of rare "escapers" from this defect varied with the genotype)]. Orientation of these units relative to genetic markers is as follows: centromere, Gas-2, pl-1, jls, jlm p, nl (equatable to cp 1 = Gabrb3); pl-2 probably resides in the c-deletion complex. pl-1 does not mask preimplantation lethals between Gas2 and p; and no genes affecting survival are located between p and cp1. The alleles specifying mottling or darker pigment (generically, pm and px, respectively) probably do not represent deletions of p-coding sequences but could be small rearrangements involving proximal regulatory elements.

Animals↗
PubMed1995

Molecular analysis of 36 mutations at the mouse pink-eyed dilution (p) locus.

Thirty-six radiation- or chemically induced homozygous-lethal mutations at the p locus in mouse chromosome 7 have been analyzed at 17 loci defined by molecular probes to determine the types of lesions, numbers of p-region markers deleted or rearranged, regions of overlap of deletion mutations, and genetic distances between loci. A linear deletion map of the [Myod1, Ldh3]-[Snrpn, Znf127] region has been constructed from the molecular analyses of the p-locus deletions. The utility of these deletions as tools for the isolation and characterization of the genes specifying the neurological, reproductive, and developmental phenotypes genetically mapped to this region will grow as more detailed molecular analyses continue.

Animals↗
PubMed1994

Phenotypic consequences of deletion of the gamma 3, alpha 5, or beta 3 subunit of the type A gamma-aminobutyric acid receptor in mice.

Three genes (Gabrg3, Gabra5, and Gabrb3) encoding the gamma 3, alpha 5, and beta 3 subunits of the type A gamma-aminobutyric acid receptor, respectively, are known to map near the pink-eyed dilution (p) locus in mouse chromosome 7. This region shares homology with a segment of human chromosome 15 that is implicated in Angelman syndrome, an inherited neurobehavioral disorder. By mapping Gabrg3 on a panel of p-locus deletions, we have determined that the order of genes within this cluster is centromere-p(D15S12h)-Gabrg3-Gabra5-Gabrb3-telom ere. Like Gabrb3, neither the Gabra5 nor Gabrg3 gene is functionally imprinted in adult mouse brain. Mice deleted for all three subunits die at birth with a cleft palate, although there are rare survivors (approximately 5%) that do not have a cleft palate but do exhibit a neurological abnormality characterized by tremor, jerky gait, and runtiness. We have previously suggested that deficiency of the beta 3 subunit may be responsible for the clefting defect. Most notably, however, in this report we describe mice carrying two overlapping, complementing p deletions that fail to express the gamma 3 transcript, as well as mice from another line that express neither the gamma 3 nor alpha 5 transcripts. Surprisingly, mice from both of these lines are phenotypically normal and do not exhibit any of the neurological symptoms characteristic of the rare survivors that are deleted for all three (gamma 3, alpha 5, and beta 3) subunits. These mice therefore provide a whole-organism type A gamma-aminobutyric-acid receptor background that is devoid of any receptor subtypes that normally contain the gamma 3 and/or alpha 5 subunits. The absence of an overt neurological phenotype in mice lacking the gamma 3 and/or alpha 5 subunits also suggests that mutations in these genes are unlikely to provide useful animal models for Angelman syndrome in humans.

Angelman Syndrome↗
PubMed1993

Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the beta 3 subunit of the type A gamma-aminobutyric acid receptor.

Genetic and molecular analyses of a number of radiation-induced deletion mutations of the pink-eyed dilution (p) locus in mouse chromosome 7 have identified a specific interval on the genetic map associated with a neonatally lethal mutation that results in cleft palate. This interval, closely linked and distal to p, and bracketed by the genes encoding the alpha 5 and beta 3 subunits of the type A gamma-aminobutyric acid receptor (Gabra5 and Gabrb3, respectively), contains a gene(s) (cp1; cleft palate 1) necessary for normal palate development. The cp1 interval extends from the distal breakpoint of the prenatally lethal p83FBFo deletion to the Gabrb3 locus. Among 20 p deletions tested, there was complete concordance between alterations at the Gabrb3 transcription unit and inability to complement the cleft-palate defect. These mapping data, along with previously described in vivo and in vitro teratological effects of gamma-aminobutyric acid or its agonists on palate development, suggest the possibility that a particular type A gamma-aminobutyric acid receptor that includes the beta 3 subunit may be necessary for normal palate development. The placement of the cp1 gene within a defined segment of the larger D15S12h (p)-D15S9h-1 interval in the mouse suggests that the highly homologous region of the human genome, 15q11-q13, be evaluated for a role(s) in human fetal facial development.

Animals↗
PubMed1982

Supermutagenicity of ethylnitrosourea in the mouse spot test: comparisons with methylnitrosourea and ethylnitrosourethane.

The effects of the 3 related compounds ethylnitrosourea (ENU), methylnitrosourea (MNU), and ethylnitrosourethane (NEC) were studied in the mouse spot test. ENU induces a large number of recessive spots (RS) and, due to its low toxicity, can be applied at relatively high doses. This combination of properties makes it the most efficient spot-test mutagen, as shown in a comparison with 16 other chemicals, even though, on the basis of molarity, it is not the most potent one. The ENU mutation frequency in cells at risk, calculated per locus, per unit of applied dose, is roughly similar for melanocyte precursors (in the spot test) and spermatogonial stem cells (in the specific-locus test). MNU which, due to its high embryotoxicity, could be tested only at a low dose, is clearly mutagenic, and dose extrapolations indicate it to be more potent than ENU. NEC, though it could be tested at higher molarities than ENU, is only weakly mutagenic. The spot test, in addition to mutational data, also yields information on cytotoxicity (white midventral spots), embryotoxicity, and teratogenicity. The toxicity and teratogenicity findings parallel earlier results in the rat. For all endpoints studied. ENU is more effective than NEC. Relative to MNU, ENU is less toxic, less teratogenic, and less mutagenic in the spot test; but it is much more carcinogenic (transplacentally) and more mutagenic in spermatogonia. We propose that MNU is more effective in inducing gross chromosomal damage than is ENU, while ENU induces relatively more gene mutations. The spot test scores both types of mutational damage, while mostly the latter type is recovered from spermatogonia.

Animals↗
PubMed1982

Analysis of the albino-locus region of the mouse: IV. Characterization of 34 deficiencies.

Thirty-four independent nonviable c-locus mutations (types cal, albino lethal and cas, albino subvital), derived from radiation experiments, were tested for involvement of nearby markers tp, Mod-2, sh-1, and Hbb: 10, 22, and 2 involved, respectively, none of these markers, Mod-2 alone, and Mod-2 plus sh-1. When classified on this basis, as well as according to developmental stage at which homozygotes die, and by limited complementation results, the 34 independent mutations fell into 12 groups. From results of a full-scale complementation grid of all 435 possible crosses among 30 of the mutations, we were able to postulate an alignment of eight functional units by which the 12 groups fit a linear pattern. Abnormal phenotypes utilized in the complementation study were deaths at various stages of prenatal or postnatal development, body weight, and reduction or absence of various enzymes. Some of these phenotypes can be separated by complementation e.g., there is no evidence that mitochondrial malic enzyme influences survival at any age); others cannot thus be separated (e.g., glucose-6-phosphatase deficiency and neonatal death).--We conclude that all of the nonviable albino mutations are deficiencies overlapping at c, and ranging in size from less than 2cM to 6-11 cM. The characterization of this array of deficiencies should provide useful tools for gene-dosage studies, recombinant-DNA fine-structure analyses, etc. Since many of the combinations of lethals produce viable albino animals that resemble the standard c/c type, we conclude (a) that the c locus contains no sites essential for survival, and (b) that viable nonalbino c-locus mutations (cxv) are the result of mutations within the c cistron. Viable albinos (cav, the majority of radiation-induced c-locus mutations) may be intracistronic mutations or very small deficiencies.

Albinism↗
PubMed1980

Use of the mouse spot test to investigate the mutagenic potential of triclosan (Irgasan DP300).

Triclosan, a chlorophenoxyphenol used in several commercial products, was tested in the mouse in vivo somatic mutation test (spot test) by intraperitoneal injection on day 9.25 or 10.25 postconception. Although the dose range tested overlapped the toxic, the frequency of presumed somatic mutations was not significantly greater in the experimental groups than in the methanol-injected controls; and the results rule out with 95% confidence a spot incidence 5 or more times greater than the control incidence. These findings fail to confirm the claim by Fahrig et al. (1978) that triclosan is mutagenic in the spot test.

Animals↗