Genetic regulation of susceptibility and severity of demyelination.
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Animals↗
Biomedical subjects
B A Taylor
Publications and source records attributed to B A Taylor.
Identification of a common ecotropic viral integration site, Evi-1, in the DNA of AKXD murine myeloid tumors.
AKXD-23 recombinant inbred mice develop myeloid tumors at a high frequency, unlike other AKXD recombinant inbred strains which develop B-cell lymphomas, T-cell lymphomas, or both. AKXD-23 myeloid tumors are monoclonal, and their DNA contains somatically acquired proviruses, suggesting that they are retrovirally induced. We identified a common site of ecotropic proviral integration that is present in the DNA of all AKXD-23 myeloid tumors that were analyzed and in the DNA of all myeloid tumors that occur in AKXD strains other than AKXD-23. We designated this locus Evi-1 (ecotropic viral integration site 1). Rearrangements in the Evi-1 locus were also detected in the DNA of a number of myeloid tumors and myeloid cell lines isolated from strains other than AKXD. In contrast, few Evi-1 rearrangements were detected in the DNA of T- or B-cell tumors. Evi-1 may thus identify a new proto-oncogene locus that is involved in myeloid disease.
Animals↗
Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.
The mouse prion protein (PrP) gene (Prn-p), which encodes the only macromolecule that has been identified in scrapie prions, is tightly linked or identical to a gene (Prn-i) that controls the duration of the scrapie incubation period in mice. Constellations of restriction fragment length polymorphisms distinguish haplotypes a to f of Prn-p. The Prn-pb allele encodes a PrP that differs in sequence from those encoded by the other haplotypes and, in inbred mouse strains, correlates with long scrapie incubation time (Westaway et al., Cell 51: 651-662, 1987). In segregating crosses of mice, we identified rare individuals with a divergent scrapie incubation time phenotype and Prn-p genotype, but progeny testing to demonstrate meiotic recombination was not possible because scrapie is a lethal disease. Crosses involving the a, d, and e haplotypes demonstrated that genes unlinked to Prn-p could modulate scrapie incubation time and that there were only two alleles of Prn-i among the mouse strains tested. All inbred strains of mice that had the Prnb haplotype were probably direct descendants of the I/LnJ progenitors. We established the linkage relationship between the prion gene complex (Prn) and other chromosome 2 genes; the gene order, proximal to distal, is B2m-II-1a-Prn-Itp-A. Recombination suppression in the B2m-Prn-p interval occurred during the crosses involved in transferring the I/LnJ Prnb complex into a C57BL/6J background. Transmission ratio distortion by Prna/Prnb heterozygous males was also observed in the same crosses. These phenomena, together with the founder effect, would favor apparent linkage disequilibrium between Prn-p and Prn-i. Therefore, transmission genetics may underestimate the number of genes in Prn.
Animals↗
Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice.
A common site of ecotropic murine leukemia virus integration designated Evi-2 (ecotropic viral integration site-2) has been identified in BXH-2 myeloid tumors. As part of experiments to determine whether Evi-2 identified a new proto-oncogene locus involved in myeloid disease, we determined its chromosomal location. We mapped Evi-2 to mouse Chromosome 11 using standard recombinant inbred strain and genetic backcross analysis. We then determined the location of Evi-2 relative to other proto-oncogene and growth factor loci located on Chromosome 11 by interspecific backcross analysis. The loci included in this study were the proto-oncogene loci, Erbb, Erba, and Rel, as well as, Il-3 (interleukin-3), Csfgm (granulocyte-macrophage colony stimulating factor), and Trp53-1 (transforming protein p53). All loci except Erbb had been previously mapped to Chromosome 11 with the use of somatic cell hybrids and consequently their positions on Chromosome 11 were not known. One proto-oncogene, Erbb-2 (analogous to the neu proto-oncogene), and one growth factor locus, Csfg (granulocyte colony-stimulating factor), which had not been mapped in the mouse were also localized on Chromosome 11 using the interspecific backcross mice. Recombination between Evi-2 and all proto-oncogene and growth factor loci was demonstrated, suggesting that Evi-2 may ultimately identify a new proto-oncogene involved in myeloid disease. This study revealed a number of interesting conserved linkage groups common to mouse and man.
Animals↗
Chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myeloid tumors.
The chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myelogenous leukemias, was determined by recombinant inbred and conventional backcross analyses. We mapped Evi-1 to a location approximately 15 cM distal to the carbonic anhydrase locus on murine Chromosome 3. The chromosomal location of the proto-oncogene Nras, and two growth factors, epidermal growth factor (Egf), and the beta subunit of nerve growth factor (Ngfb), which had previously been assigned to Chromosome 3 by somatic cell hybrid analysis, were also determined. The location of Evi-1 is distinct from these three loci and from all other proto-oncogenes, common sites of viral integration, or growth factor loci previously mapped in mouse chromosomes. These results suggest that Evi-1 represents a new locus involved in myeloid disease.
Animals↗
Genetic factors controlling structure and expression of apolipoproteins B and E in mice.
We report the identification and partial characterization of polymorphisms among inbred strains of mice affecting several aspects of the expression of apolipoproteins B and E (apoB and apoE), the major proteins of low density lipoproteins (LDL) and very low density lipoproteins (VLDL). These polymorphisms include differences in the levels of the lipoproteins and apolipoproteins on both chow and high fat diets, differences in their response to a high fat diet challenge, and differences in the relative levels of the two molecular weight species of apoB. Although most strains exhibited a large increase in plasma LDL and VLDL in response to a high fat diet, the levels of apoB and apoE mRNA were either unaffected or, in some cases, decreased slightly. Also, the levels of apoB and apoE mRNA were not correlated among strains with the levels of the apolipoproteins in plasma, suggesting that genetic control occurs primarily at the level of lipoprotein catabolism. Elucidation of the precise mechanisms involved in the differences will require genetic analysis. Toward this end, we have identified DNA polymorphisms for apoB and apoE and have used these in segregation analysis to determine the chromosomal locations of the apoB and apoE structural genes in mice. The gene for apoB, designated Apob, resides in the proximal region of chromosome 12 linked to genes for ribosomal RNA and aryl hydrocarbon hydroxylase. The gene for apoE, designated Apoe, is located on chromosome 7, linked to genes for glucose phosphate isomerase and peptidase 4. Previously, we mapped the structural genes for apolipoproteins A-I and A-II to mouse chromosomes 9 and 1, respectively, and thus, the four loci encoding mammalian apolipoproteins have now been located in the mouse. These loci are homologous to the loci encoding apolipoproteins in humans as judged by the conservation of linked markers. A correlation was observed between a unique apoB allele and "responsiveness" to a high fat diet challenge. There were no obvious associations of apoB, apoE, or LDL/VLDL phenotypes or genotypes with diet-induced atherosclerosis among strains surveyed. These results clarify the organization and regulation of the genes for apoB and apoE, and they provide information about the naturally occurring polymorphisms affecting their expression.
Animals↗
Mouse DNA 'fingerprints': analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains.
Human minisatellite probes cross-hybridize to mouse DNA and detect multiple variable loci. The resulting DNA "fingerprints" vary substantially between inbred strains but relatively little within an inbred strain. By studying the segregation of variable DNA fragments in BXD recombinant inbred strains of mice, at least 13 hypervariable loci were defined, 8 of which could be regionally assigned to mouse chromosomes. The assigned loci are autosomal, dispersed and not preferentially associated with centromeres or telomeres. One of these minisatellites is complex, with alleles 90 kb or more long and with internal restriction endonuclease cleavage sites which produce a minisatellite "haplotype" of multiple cosegregating fragments. In addition, one locus shows extreme germ-line instability and should provide a useful system for studying more directly the rates and processes of allelic variation of minisatellites.
Animals↗
The structural gene for F liver protein (Flp) maps to chromosome 5 of the mouse.
The BXD and AKXL panels of recombinant inbred mouse strains have been typed for the F liver protein alloantigen. The structural gene for F liver protein gene (Flp) is placed on the distal part of chromosome 5, between the known markers Bcd-1 and Gus-s. This excludes the possibility that F liver protein is a major histocompatibility complex molecule, and in turn raises a question about the uniqueness of F and certain other proteins as purgers of self-reactivity among T but not B cells. The typed RI strains have then been used for the immunogenetic studies presented in the succeeding article.
Animals↗
Localization of the inosine triphosphatase locus (Itp) on chromosome 2 of the mouse.
An electrophoretic variant of the enzyme inosine triphosphatase was found by screening inbred strains of mice. Strains with the slower-migrating variant include BALB/cJ, DBA/1J, and PL/J. The Itp locus was mapped between the beta-2-microglobulin (B2m) and the agouti (a) loci on chromosome 2. The mapping of Itp on chromosome 2 identifies a chromosomal segment that has been conserved since the divergence of lineages leading to mouse and man.
Animals↗
Esterase-25 (Es-25): identification and characterization of a new kidney arylesterase of the house mouse, genetically linked to Ly-18 on chromosome 12.
Genetic variation of a codominantly inherited kidney esterase, designated ES-25, has been discovered in the house mouse using disc electrophoresis. The ES-25A phenotype was found in A strains, AKR, and BALB/c. ES-25B was found in C57BL strains and several other laboratory strains. The enzyme was shown to be controlled by a presumed structural locus, Es-25. The high concordance in 48 RI strains of Es-25 with Ly-18 indicated the location of Es-25 on chromosome 12. The gene order Es-25-Ly-18-D12Nyul-Pre-1 was proposed.
Animals↗
The J ileal pouch-anal anastomosis.
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Anal Canal↗
Perforation of terminal ileal appendage of J-pelvic ileal reservoir.
If, during restorative proctocolectomy, the most distal segment of the terminal ileum is not incorporated into the reservoir during J-pouch construction, it will remain as an appendage and may twist upon itself and obstruct. Two cases in which this resulted in significant complications are described.
Adult↗
Colonic lipomas. Report of two unusual cases and review of the Mayo Clinic experience, 1976-1985.
Two cases of symptomatic submucosal lipomas of the large intestine are described. One occurred in a patient with familial multiple lipomatosis causing an intussusception and intermittent obstruction. The other caused subacute obstruction and rectal bleeding and was thought to represent a carcinoma. These two cases closely resemble those few patients with symptomatic lipomas of the colon that make up a small subgroup (6 percent) of a series of 91 patients with this diagnosis managed surgically at the Mayo Clinic between the years 1976 to 1985. The majority of patients in this series had lipomas that were entirely incidental findings usually associated with more significant pathology that dictated the operative procedures undertaken. Lipomas themselves may be managed by local excision only although segmental resection may be necessary in isolated cases.
Aged↗
Mapping of the mouse fibronectin gene (Fn-1) to chromosome 1: conservation of the Idh-1-Cryg-Fn-1 synteny group in mammals.
Restriction fragment length polymorphisms (RFLPs) were observed in BamHI-digested mouse DNA probed with a cDNA for human fibronectin. Analysis of the inheritance of fibronectin RFLPs in AKXD and SWXJ recombinant inbred strains of mice mapped the locus, Fn-1, to the midregion of mouse chromosome 1 about 4 cM distal from the loci encoding gamma-crystallins (Cryg). Loci homologous to genes in the centromeric third of mouse chromosome 1 are also syntenic in rats, humans, and cattle and may, therefore, mark a large conserved chromosomal segment of the mammalian genome.
Animals↗
Relationship of the genes for Chediak-Higashi syndrome (beige) and the T-cell receptor gamma chain in mouse and man.
The genetic linkage of Chediak-Higashi syndrome and its murine analog, beige (bg), to the T-cell receptor (TCR-gamma) gamma chain gene is further defined. Previous studies using recombinant inbred strains of mice demonstrated that the murine bg gene is genetically linked to a murine TCR-gamma gene. We report that in the mouse the frequency of recombination between these two markers is 0.025. Further, we tested the hypothesis that these two genes are linked in the human genome by analyzing restriction fragment length polymorphisms (RFLPs) in five families with children afflicted with Chediak-Higashi syndrome. In three families, RFLPs in TCR-gamma genes were inherited discordantly from Chediak-Higashi syndrome, demonstrating nonlinkage. We postulate that there is an evolutionary chromosomal breakpoint between the bg gene and the TCR-gamma gene.
Animals↗
The congenital goiter mutation is linked to the thyroglobulin gene in the mouse.
Rat thyroglobulin (TG) cDNA clones were used to identify DNA restriction fragment variants among inbred mouse strains. One of these variants was shown to be closely linked to the recessive mutation congenital goiter (cog), which had previously been mapped to mouse chromosome 15. These results indicate that the structural gene for thyroglobulin is on chromosome 15 and suggest that a mutation at the site of the TG gene is the basis of the cog defect. No differences were observed between cog/cog and +/+ DNA in Southern blots using TG cDNA probes corresponding to 88% of the coding sequences, suggesting that the cog mutation is not due to a large deletion of this portion of the gene. Neither was there any obvious qualitative or quantitative difference between mutant and normal TG mRNA as judged by blot hybridization of electrophoretically fractionated thyroid RNAs. The thyroglobulin gene locus (Tgn) was mapped near the glutamic-pyruvic transaminase isoenzyme locus Gpt-1. The Tgn locus is syntenic with the c-myc protooncogene locus (Myc) in the mouse as in the rat and man.
Animals↗
The genes for mouse salivary androgen-binding protein (ABP) subunits alpha and gamma are located on chromosome 7.
We demonstrate that the previously described gene Androgen binding protein (Abp; Dlouhy and Karn, 1984) codes for the Alpha subunit of ABP and rename the locus Androgen binding protein alpha (Abpa). A study of recombinant inbred strains demonstrates that Abpa is located on chromosome 7 near Glucose phosphate isomerase-1 (Gpi-1). Biochemical and genetic evidence indicates the existence of another ABP subunit, Gamma, and its locus, Androgen binding protein gamma (Abpg), that is closely linked to Abpa. Although no polymorphism has yet been found for the previously described Beta subunit of ABP (Dlouhy and Karn, 1983; 1984), we suggest that it represents a third locus. Androgen binding protein beta (Abpb). ABP subunits appear to dimerize randomly and a model is presented demonstrating the origin of six ABP dimers in the salivas of AbpaaAbpga/AbpabAbpgb heterozygous mice. The results of cell-free translation studies in which the pre-ABP subunits are identified specifically by immunoprecipitation with anti-ABP antibody supports the idea that independent mRNAs code for the Alpha, Beta and Gamma subunits.
Androgen-Binding Protein↗
Characterization of somatically acquired ecotropic and mink cell focus-forming viruses in lymphomas of AKXD recombinant inbred mice.
The DNA of lymphomas from 12 AKXD recombinant inbred mouse strains was analyzed to determine the presence of somatically acquired ecotropic and mink cell focus-forming proviruses. Mink cell focus-forming proviruses were associated primarily with T-cell lymphomas, whereas ecotropic proviruses were associated with lymphomas of B-cell and myeloid lineages. A model based on the results is proposed to explain the variation in lymphoma types observed in different AKXD strains.
Alleles↗