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Biomedical subjects

M Potter

Publications and source records attributed to M Potter.

At least 163 records · Page 9Linked to original sources
PubMed1988

The Ig kappa L chain allelic groups among the Ig kappa haplotypes and Ig kappa crossover populations suggest a gene order.

The Ig kappa complex locus of inbred mice found on chromosome 6 contains one constant (C kappa), five joining (J kappa), and 100 to 300 variable (V kappa) exons and spans an estimated 500 to 2000 kbp of DNA. The V kappa exons are organized into groups of highly homologous coding regions (approximately 300 bp) separated by approximately 10 kbp of intervening sequence. A group contains from 1 to 30 or more exons (exon refers to uninterrupted coding region DNA which is capable of encoding all or part of V kappa gene) that can be detected with specific DNA probes in conjunction with restriction endonuclease fragments (REF) from genomic DNA. Thirteen DNA probes specific for different V kappa exon groups and one DNA probe specific for J kappa and C kappa exons were used in conjunction with 55 inbred strains in an attempt to detect RFLP that could be used to establish Ig kappa allelic groups and Ig kappa haplotypes. Each probe detected two to four different REF patterns (allelic groups) among the panel of inbred mice examined. Size estimates of the REF were made, and each probe detected 4.2 to 107.7 kbp of DNA, including faint REF, 675.6 to 723.6 kbp of DNA could be detected within a single haplotype. Based on these allelic groups, seven haplotypes were identified among the 55 inbred strains of mice. No subline differences were detected, and the distribution of allelic groups implied common ancestry among many of the inbred strains examined. The DNA probes were also used in conjunction with recombinant inbred, congenic strains and backcross populations of mice. By using the analysis of known Ig kappa r populations, and assuming a common ancestry among the inbred strains, a gene order was predicted: Centromere-Hd-(Ig kappa-V11, Ig kappa-V24, Ig kappa-V9-26)-(Ig kappa-V1, Ig kappa-V9)-(Ig kappa-V4, Ig kappa-V8, Ig kappa-V10, Ig kappa-V12, 13, Ig kappa-V19)-(Ig kappa-V28, Rn7s-6)-Ig kappa-V23-(Ig kappa-V21, Ig kappa-J, Ig kappa-C)-(Ly2, Ly3)-wa-1.

Alleles↗
PubMed1988

Myc-1 is centromeric to the linkage group Ly-6--Sis--Gdc-1 on mouse chromosome 15.

A survey of wild mouse DNA with a c-myc exon 1 probe revealed a Taq I restriction fragment length polymorphism (RFLP) among Mus species. As a result of this Taq I RFLP, a cross between Mus musculus domesticus and BALB/cJ permitted the positioning of Myc-1 on chromosome 15 with respect to Ly-6, Sis, and Gdc-1. Compilation of the recombination frequency generated from this cross with published cytogenetic and plasma-cytoma somatic cell hybrid data suggests the following chromosome 15 orientation: centromere--Myc-1--Ly-6--Sis--Gdc-1--telomere. This gene order is consistent with conservation of man-mouse synteny.

Animals↗
PubMed1988

Molecular genetics and heterogeneity in manic depression.

Recent research has shown that there are X-linked and possibly chromosome 11-linked forms of manic depression as well as at least one other autosomal form. Segregation analyses of large affected families and the finding of genetic linkage between chromosome specific markers and manic depression mutations provide strong evidence that bipolar as well as unipolar forms of manic depression (MD) within the same family are inherited as a dominant gene disorder. This clarification of the etiology of certain types of depression should bring changed attitudes within psychiatry and may serve to stimulate discussion of the role of evolutionary mechanisms. From a clinical point of view, it has now become possible to determine whether clinical (phenotypic) variation reflects the underlying genotypic heterogeneity of linkage. A preliminary analysis of data from four recent studies shows that there is no clear correlation between such clinical features as the ratio of unipolar to bipolar cases and the genotypic form of manic depression. Further recombinant DNA research, proven to be successful in other genetic diseases, can soon be applied to manic depression. The specific problems posed by manic depression for these techniques are discussed.

Bipolar Disorder↗
PubMed1988

Genes on chromosomes 1 and 4 in the mouse are associated with repair of radiation-induced chromatin damage.

Early-passage skin fibroblasts from different inbred and congenic strains of mice were X-irradiated (1 Gy), and the number of chromatid breaks was determined at 2.0 h after irradiation. The cells from DBA/2N, C3H/HeN, STS/A, C57BL/6N, BALB/cJ, and AKR/N had 25 to 42 chromatid breaks per 100 metaphase cells (efficient repair phenotype). NZB/NJ had greater than 78 and BALB/cAn had 87 to 110 chromatid breaks per 100 cells (inefficient repair phenotype). Differences between BALB/cAn and BALB/c. DBA/2 congenic strains which carry less than 1% of the DBA/2 genome indicate that two genes, one on chromosome 1 linked to bcl-2-Pep-3 and the other on chromosome 4 closely linked to Fv-1, affect the efficiency with which the cells repair radiation-induced chromatin damage.

Animals↗
PubMed1988

Rapid induction of IgM-secreting murine plasmacytomas by pristane and an immunoglobulin heavy-chain promoter/enhancer-driven c-myc/v-Ha-ras retrovirus.

A retroviral vector, RIM, containing murine c-myc under the control of immunoglobulin heavy-chain gene promoter and enhancer elements and v-Ha-ras driven by a Moloney murine leukemia virus long terminal repeat induced IgM-secreting plasmacytomas in 28% of adult and 83% of 3-week-old pristane-conditioned mice with mean latency periods of 60-70 days. In contrast, the same vector only harboring c-myc or v-Ha-ras was virtually ineffective. RIM-induced plasmacytomas expressed retroviral myc and ras genes while their endogenous c-myc alleles were unrearranged and transcriptionally inactive. These plasmacytomas were clonal as each possessed a unique immunoglobulin heavy-chain joining region rearrangement and a single recombinant provirus. Moloney murine leukemia helper virus did not play an obligatory role in tumorigenesis since insertions of Moloney murine leukemia proviruses were found in only 6 of 24 plasmacytomas induced in adult mice. Taken together, these findings support the view that the v-Ha-ras oncogene can cooperate with an activated myc gene in pristane plasmacytomagenesis.

Animals↗
PubMed1988

Activated neutrophils induce prolonged DNA damage in neighboring cells.

We have measured the capacity of highly-purified, paraffin oil-elicited neutrophils to induce DNA single-strand breaks in a newly established plasmacytoma cell line, RIMPC 2304, which was induced by a retrovirus containing the c-myc and V-Ha-ras oncogenes. This cell line effectively repairs DNA damage induced by gamma-irradiation. DNA damage induced by neutrophils was correlated with the oxidative burst of the neutrophils. The levels of superoxide anion, H2O2, and HOCl produced after stimulation of the neutrophils (6 X 10(5)/cm3) with the tumor promoter phorbol myristate acetate (100 nM) were 33.8 microM, 12.8 microM and 1.7 microM respectively in 15 min, and 98 microM, 20 microM and 8.7 microM respectively in 90 min. The results of alkaline elution experiments revealed that when the same concentration of neutrophils was co-incubated for 15 min in serum-free medium with an equal number of radioactively labeled RIMPC 2304 cells, the latter incurred a level of damage that approximated that caused by 300 rad equivalents of gamma-irradiation or by a 1-min treatment with 20 microM H2O2 at 37 degrees C. Damage from neutrophils was coincident with the oxidative burst; it was induced rapidly (within 5 min) but remained high for more than 90 min. The level of damage achieved was dependent upon the ratio of neutrophils: target cells and was clearly detectable at ratios as low as 0.25:1. Induction of single-strand breaks was completely inhibited by catalase and partially inhibited by superoxide dismutase, mannitol, and reduced glutathione but not by Na azide. Addition of the non-steroidal anti-inflammatory drug indomethacin either enhanced (at 50 microM) or had no effect (at 2 microM) on the damage detected. Finally, repair of strand breaks induced by neutrophils was significantly slower (half-time approximately 10 min) than that observed for repair of similar levels of damage induced by H2O2 or gamma-irradiation (half-times approximately 3 min, each). The results indicate that neutrophils cause prolonged DNA damage in neighboring cells. Moreover, they indicate that although H2O2 produced in the oxidative burst is an essential mediator of the damage observed, additional reactive oxygen intermediates including the superoxide anion are also implicated. The data are discussed in relation to the possible role of neutrophils in chronic inflammation and in pristane-induced plasmacytoma formation in mice.

Animals↗
PubMed1988

Chromosomal location of the regulator of mouse alpha-fetoprotein, Afr-1.

Afr-1 is a gene whose product contributes to the adult regulation of mouse alpha-fetoprotein (AFP). In Afr-1b/b homozygotes, the adult serum levels of AFP are 10- to 20-fold higher than in Afr-1a/a or Afr-1a/b mice. The studies reported here were performed to map the Afr-1 gene. Our results show that Afr-1 resides on mouse chromosome 15, approximately 25 cM from Gdc-1. Afr-1 appears to be located in close proximity to the mouse c-myc oncogene. These results are discussed with respect to the susceptibility or resistance of different BALB/c sublines (which are either Afr-1a or Afr-1b, respectively) to pristane-induced plasmacytomas.

Animals↗
PubMed1988

Genes that modify expression of major urinary proteins in mice.

A survey of major urinary proteins (MUPs) from eight BALB/c mouse substrains by isoelectric focusing identified a common pattern with about 10 protein bands in males. One substrain, BALB/cJPt, differed in that it expressed two variant MUP patterns, designated 4.1lo and null. To find the chromosomal location of the gene which determines the 4.1lo phenotype, BALB/cJPt-MUP-4.1lo was crossed with a wild-derived Mus musculus domesticus inbred strain (CLA) that expresses the common BALB/c MUP pattern. The F1 phenotype revealed that the gene(s) controlling the MUP-4.1lo trait was recessive. A restriction fragment polymorphism between these strains found with a MUP cDNA probe allowed us to establish that a gene determining the MUP-4.1lo trait was not linked to the MUP structural genes on chromosome 4. Assays for other chromosomal marker loci revealed that a gene determining the MUP-4.1lo trait, designated Mupm-1, was closely linked to Myc-1 on chromosome 15. To determine the genetic basis of the null trait, BALB/cJPt-MUP-null mice were crossed with BALB/cJPt-MUP-4.1lo mice. A MUP restriction fragment polymorphism between these two lines was tightly linked to a gene or genes involved in determining the MUP-null phenotype. The two variant MUP phenotypes in BALB/cJ mice are determined by separate genes, one of which is located on chromosome 4 and the other on chromosome 15. The chromosomal location of Mupm-1 suggests that it produces a trans-acting factor which regulates MUP expression.

Animals↗