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T H Roderick

Publications and source records attributed to T H Roderick.

At least 55 records · Page 3Linked to original sources
PubMed1987

Different genes specify hyporesponsiveness to seizures induced by caffeine and the benzodiazepine inverse agonist, DMCM.

Two strains of inbred mice differed significantly in their susceptibility to tonic seizures induced by caffeine and the benzodiazepine inverse agonist, methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). The hyporesponsive strain, SWR, was not less susceptible to the convulsant action of other chemical convulsants, an observation which indicated that the response differences between the strains were pharmacologically specific. These observations and drug interaction studies suggested that caffeine-induced seizures might be mediated through an "inverse" agonist-like action of caffeine on benzodiazepine receptors associated with GABA receptor-benzodiazepine receptor-chloride ionophore complex. To determine whether the coincident alteration in susceptibility to DMCM and caffeine resulted from a single mutational change or was the result of two different genetic changes occurring coincidentally between these two strains of mice, progeny from conventional Mendelian crosses (F1, F2 and reciprocal backcrosses) were analyzed for the co-segregation of susceptibility to DMCM and caffeine. The inheritance of DMCM sensitivity was consistent with a single autosomal gene determinant in which the allele specifying increased responsiveness was dominant to the allele determining hyporesponsiveness. The frequent occurrence of recombinant phenotypes (e.g., caffeine hyporesponsive but DMCM sensitive mice) among F2 and backcross progeny established that different genetic determinants encode DMCM susceptibility and caffeine susceptibility in these two strains of mice. Thus, while these data establish a simply inherited difference in benzodiazepine responsiveness between the two mouse strains, they also indicate that this pair of strains is inappropriate for a genetic analysis aimed at probing the relationship between caffeine-induced seizures and the benzodiazepine receptor.

Animals↗
PubMed1986

Electroretinograms in carriers of blue cone monochromatism.

We recorded full-field electroretinograms from seven female obligate carriers of X-linked blue cone monochromatism and eight daughters of obligate carriers. We observed that all obligate carriers had one or more of the following abnormalities: delayed cone b-wave implicit times to 30-Hz white flicker, loss of the a1 oscillation in responses to single flashes of white light under dark-adapted conditions, subnormal b-wave amplitudes to single flashes of white light under dark-adapted conditions, and subnormal cone responses to 30-Hz white flicker. All had normal rod responses to blue light. Three of eight daughters of obligate carriers had abnormal electroretinograms comparable to those recorded from obligate carriers. These obligate carriers have a partial but comparable deficiency of red and green cone function.

Adult↗
PubMed1986

Complex genetic determinants of susceptibility to methylxanthine-induced locomotor activity changes.

The intent of this study was to investigate the role of inheritance in the determination of susceptibility to methylxanthine-induced behavioral changes. Two strains of inbred mice, SWR and CBA, which differ significantly in their response to caffeine- and theophylline-induced stimulation of locomotor activity, were used in classical genetic crosses to produce reciprocal F1 hybrids, reciprocal backcross progeny F2 progeny. Theophylline dose response curves in the reciprocal F1 hybrid strains were identical to each other and to their methylxanthine-responsive (CBA) parent. These results indicated that theophylline responsiveness behaved as a simple autosomal dominant trait. Behavioral responses of these F1 hybrid strains to caffeine showed the same maximal enhancement of locomotor activity as their CBA progenitor at a dose 10 mg/kg IP, but locomotor activity stimulation also occurred at 32 mg/kg IP, a dose which inhibited their CBA parent. These data suggest that the genes specifying caffeine responsiveness differ from those encoding theophylline responsiveness. For both caffeine and theophylline, behavioral phenotypes and their expected frequencies of occurrence among backcross and F2 progeny differed significantly from the segregation ratios expected for a trait determined by a single gene. These non-Mendelian segregation ratios suggest that locomotor activity stimulation by both of these methylxanthines is polygenically determined. It was anticipated that the same genetically encoded neurochemical mechanism would underlie the difference in behavioral response to the two methylxanthines. However, no significant correlation between caffeine-induced and theophylline-induced stimulation of locomotor activity was observed among progeny derived from backcrosses of F1 self-crosses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

A single gene difference determines relative susceptibility to caffeine-induced lethality in SWR and CBA inbred mice.

Inbred mouse strains SWR and CBA differ markedly in their relatively susceptibility to the acute toxic effects of intraperitoneally administered caffeine. At a dose of 187 mg/kg, SWR mice survive a stress-potentiated lethality test apparently related to the generation of tonic seizures; in contrast, CBA mice usually die in less than 30 seconds after this dose. Progeny from several different genetic crosses were characterized to determine the genetic basis underlying this phenotypic difference in caffeine sensitivity. F1 progeny from reciprocal crosses of the parental strains were uniformly sensitive to caffeine-induced lethality, i.e., caffeine responsiveness behaves like an autosomal dominant trait. Self-crossing of F1 individuals produced both progeny which were resistant to caffeine-induced lethality (26% of the total) and those which were susceptible (74%). Backcrosses of the F1 animals to the CBA parent produced no (0/19) resistant progeny. In contrast, backcrosses of F1 animals to SWR produced 54% resistant progeny. These data indicate that the difference in susceptibility to caffeine-induced lethality between these strains is determined by a single pair of autosomal alleles in which susceptibility (responsiveness) to this methylxanthine is dominant to resistance (nonresponsiveness).

Animals↗
PubMed1985

Genetic and developmental studies of a new mouse mutation that produces otocephaly.

A new recessive lethal mutation in mice that produces the otocephaly defect is described. The mutation, provisionally named oto is located on chromosome 1, within, or just outside of, a previously existing inversion, In(1)1Rk, and was probably induced by X-irradiation. The penetrance of oto is nearly complete on C57BL strain backgrounds but is reduced to a variable extent on other backgrounds. The previously reported liability to spontaneous otocephaly in the C57BL strains appears to increase the penetrance of oto. Studies of the sequences of developmental changes (conducted primarily by scanning electron microscopy) and of the range of defects indicate that a primary deficiency involving the anterior aspect of the embryonic disc occurs in affected individuals. An hypothesis related to deficiencies in mesodermal populations is presented as the basis for the craniofacial and brain defects observed.

Animals↗
PubMed1984

Prevalence of retinitis pigmentosa in Maine.

Between 1976 and 1980, medical and social service sources were used to ascertain cases of retinitis pigmentosa in Maine (1980 population, I, 124,660). As of July 1, 1980, 241 clinically prevalent cases of retinitis pigmentosa were ascertained. Extensive pedigrees were collected for 185 of the subjects and medical records were obtained. One hundred fourteen cases were further evaluated by clinical examination including electroretinography. Adjusting for incorrect diagnosis (eight of 114, 7%) and underascertainment (23 of 185, 12.5%), we estimated that prevalence of retinitis pigmentosa in Maine is 236 cases, 21 per 100,000 population or 1:4,756. Excluding Usher and Bardet-Biedl syndromes, the prevalence is 1:5,193. Estimated birth incidence of persons who will become affected with non-syndrome retinitis pigmentosa is 1:3,544. Incidence of newly diagnosed cases per year is about six per 1,000,000 population. Among kindreds, 16 of 85 (19%) were autosomal dominant, 55 of 85 (65%) autosomal recessive or isolated cases, seven of 85 (8%) X-linked recessive, and seven of 85 (8%) not classified by mode of transmission.

Adolescent↗
PubMed1982

Synaptonemal complex analysis of mouse chromosomal rearrangements. IV. Synapsis and synaptic adjustment in two paracentric inversions.

Two paracentric inversions in the mouse, In (1) 1 Rk and In (2) 5 Rk, have been studied in surface microspreads of spermatocytes from heterozygotes. At zytogene, synaptic initiation occurs independently in three regions: within the inversion, and without, on either side. Synaptonemal complex (SC) formation is restricted to homologous regions, resulting in inversion loops in all early pachytene spermatocytes. An adjusting phase then occurs during pachytene in which the inversion loop is reduced by desynapsis of homologously synapsed SC, followed immediately by non-homologous synapsis with the alternate pairing partner, progressing from the ends toward the middle. Adjustment occurs during the first half of pachytene, but is not closely synchronized with sub-stage. It is complete by late pachytene, the loop having been eliminated in all cases and replaced by "straight" SCs in which the inverted region is heterosynapsis. Synapsis in the adjustment phase is evidently permitted only after the homosynaptic phase, and is indifferent to homology. It may lead to hetersynapsis, as in the inversion region, or to synapsis of homologous regions not synapsed at zytogene. The anaphase bridge frequency, a measure of crossing over within the inversion, is about 34% for both inversions studied, indicating that such crossovers do not block adjustment, that crossing over probably occurs before or during the adjustment period, and that there is some crossover suppression. The last could be the consequence of blocking by desynapsis/heterosynapsis. Synaptic adjustment appears to be a general phenomenon that occurs to varying extents in different forms. A hypothetical scheme for two phases of synapsis is proposed: at zytogene, a basic propensity for indifferent SC formation is limited by a restricting condition to synapsis between homologous regions, Subsequently, the restriction is lifted, whereupon synaptic instability is resolved by desynapsis, followed by resynapsis that is indifferent to homology, but that results in a topologically more stable structure.

Animals↗
PubMed1982

Pleiotropic and other genetic effects influencing the activities of brain and liver enzymes in congenic lines of C57BL/6J mice with defined electrophoretic variant markers.

A single genetic factor may affect the realization of several enzymes. To investigate the extent of pattern pleiotropy in the mouse, the activities of 28 enzymes in livers and brains from an inbred stock of C57BL/6JNctr and five F1 stocks heterozygous for known electrophoretic variants were measured. Five congenic backcross stocks of C57BL/6J, each homozygous for one or more electrophoretic markers, were mated with C57BL/6JNctr to construct the heterozygous variant F1 stocks. One of the five F1 stocks had no enzyme activities significantly different from those of C57BL/6JNctr, while two had one enzyme, one had four enzymes, and another had six enzymes with activities that were significantly different from those of C57BL/6JNctr. The latter two F1 stocks with multiple activity differences were those having the largest proportion of their genome of donor origin. Two of the F1 stocks were different from each other for one enzyme, and two were different for another enzyme. These differences and the relationship of these enzyme activities to the variant genes suggest that several genetic factors may affect an enzyme's realization.

Animals↗
PubMed1981

Synaptonemal complex analysis of mouse chromosomal rearrangements. III. Cytogenetic observations on two paracentric inversions.

Synaptonemal complex (SC) analysis by electron microscopy of spermatocytes in surface microspreads was carried out in mice heterozygous for two paracentric inversions: either In(1) 1 RK or In(2)5Rk. characteristic SC inversion loops are formed at synapsis in bivalents carrying the rearrangements. Although all loops were observed to be eliminated by late pachytene through synaptic adjustment, every spermatocyte at early pachytene contained a fully synapsed loop. Cells in the earliest stage of pachytene contained the longest loops and thus had undergone minimal adjustment. The SC estimates of inversion lengths and breakpoint positions in such cells corresponded well with those from mitotic chromosome banding and could be correlated with genetic maps of chromosomes #1 and #2, thus demonstrating the basis for the mapping of pachytene chromosomes. The regularity of loop formation and reproducibility of the SC analysis are reflected in the constant relative positions of the estimated breakpoints. The method is sensitive enough to reflect small, real, interstitial length differences between meiotic and mitotic chromosomes. The results demonstrate the feasibility and precision of detection and quantitative characterization of inversions at early meiotic prophase by SC analysis.

Animals↗
PubMed1981

A pericentric inversion in the mouse.

A pericentric inversion induced in a Robertsonian chromosome was recovered and analyzed in a male heterozygous for the rearrangement. Identification was made from chromosome banding and confirmed by synaptonemal complex(SC) analyses. From the former, the chromosome was identified as Rb4Bnr. The inversion involves about 34% of the chromosome length, and is designated In(11.13LS)29Rk. Analysis of SC inversion loops gave break points at 0.20 in the short arm and 0.54 in the long arm. Inhibition of homologous synapsis in the inversion was observed at zygotene and early pachytene, while synaptic adjustment was found to lead to heterologous SC formation at late pachytene. The inversion is believed to be causally related to the reduction in fertility observed in the carriers.

Animals↗