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21.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
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Ovine T-cell lines (including one clone [101A]), which are specific for Bluetongue virus serotype 1 (BTV1), have been established and characterized. Although these T-cell lines react with different isolates of BTV1 (including those from South Africa, Australia, Nigeria, and Cameroon), they do not react with heterologous BTV serotypes. Antigen specificity of these T-cells was studied using purified virus particles, infectious subviral particles (ISVP) and cores, or using individual BTV structural proteins that were either isolated by SDS-PAGE or expressed by recombinant strains of vaccinia virus. The results showed that each of the T-cell lines reacted with outer capsid protein VP2 (the BTV protein exhibiting most serotype-specific variation and the major neutralization antigen). However, all of the uncloned T-cell lines also reacted with either the core structural proteins or the outer capsid protein VP5. In contrast, the T-cell clone 101A only reacted with outer capsid protein VP2. Cell surface marker analysis showed that 101A has a helper T-cell phenotype (CD5+, CD4+, CD8-, T-19-). The T-cell lines and clone 101A all produced large amounts of interleukin 2 (IL-2) when stimulated with purified BTV1 virus particles, or with VP2 (up to 120 IU/ml from 2 x 10(5) T-cells). BTV serotype-specific antigenic sites, for B cells and at least one site for ovine helper T-cells, are therefore located within VP2. 相似文献
24.
25.
Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. 总被引:10,自引:0,他引:10
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C. D. Fletcher M. Akerman P. Dal Cin I. de Wever N. Mandahl F. Mertens F. Mitelman J. Rosai A. Rydholm R. Sciot G. Tallini H. van den Berghe W. van de Ven R. Vanni H. Willen 《The American journal of pathology》1996,148(2):623-630
Soft tissue tumors commonly show cytogenetic abnormalities, some of which are tumor specific. Lipomatous tumors represent the largest category of soft tissue neoplasms, and numerous karyotypic aberrations have been identified. However, clear-cut correlation between morphology and karyotype has not been undertaken on a systematic basis in a double-blind setting. The morphological features and histological diagnosis of 178 lipomatous neoplasms were reviewed independently without knowledge of the clinical data. The consensus diagnoses were then correlated with the clinical findings and compared with the tumors' karyotypes, using G-banded preparations from short-term cultures. The data were collated by a multicenter collaborative group of pathologists, geneticists, and surgeons. Clonal chromosomal abnormalities were identified in 149 cases studied (84%) and, to a large extent, the karyotype correlated with the morphological diagnosis. Specifically, 26 (96%) of 27 myxoid liposarcomas and its poorly differentiated variants showed a t(12;16); 29 (78%) of 37 atypical lipomatous tumors (including 5 dedifferentiated cases) showed ring chromosomes; 74 (80%) of 93 subcutaneous and intramuscular lipomas had karyotypic aberrations affecting mainly 12q, 6p, and 13q; 7 of 8 spindle cell and pleomorphic lipomas had aberrations of 16q; 3 lipoblastomas showed 8q rearrangements; and 2 hibernomas showed 11q abnormalities. We conclude that cytogenetic abnormalities are common in lipomatous tumors, correlate reliably with morphological sub-type in many cases, and can be of diagnostic value in histologically borderline or difficult cases. 相似文献
26.
Th. Mertens Carola Zippel R. Seuffer H. J. Eggers 《Medical microbiology and immunology》1983,172(3):181-189
Four different tests for detection of rubella-specific IgM antibodies were compared: two Ig separation methods (centrifugation and chromatography) with subsequent haemagglutination inhibition test and two commercially available ELISA tests. The 114 sera tested had been sent to the diagnostic laboratory, mostly with insufficient clinical histories. Agreement between the centrifugation method and one of the ELISA tests was good (2 divergent results with 107 sera tested), while the other ELISA test yielded more positive (partly perhaps non-specific) results. The chromatographic method did not separate the Ig classes as reliably as the centrifugation method, but because of its simplicity it may be useful, if adequate test controls are performed. The divergent results are discussed. It is postulated that in cases with pending induced abortion, two independent tests should be performed. 相似文献
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28.
It is well recognized that the ability to cryopreserve unfertilizedhuman oocytes would make a significant contribution to infertilitytreatment. However, despite considerable interest, very fewsuccessful pregnancies have arisen from cryopreserved oocytesafter thawing, insemination and transfer of the subsequent embryo.The reasons for this lack of progress may well result from adearth of information on how the various biophysical changesduring a cryopreservation regimen affect human oocyte function.Recently, fundamental studies on the effects of cooling, membranepermeability, cryoprotectant addition and ice formation havebeen performed on human oocytes by a number of groups, and theseform the basis of the current review. It is likely that successfulhuman oocyte cryopreservation will only follow once these factorsare fully understood, but the existing base of knowledge shouldprovide a platform for further improvements in the techniquescurrently employed. 相似文献
29.
30.
Clonal chromosome abnormalities in two liposarcomas 总被引:4,自引:0,他引:4
F Mertens B Johansson N Mandahl S Heim K Bennet A Rydholm H Willén F Mitelman 《Cancer Genetics and Cytogenetics》1987,28(1):137-144
Two liposarcomas were analyzed with chromosome banding technique. The sole chromosomal abnormality in one of the tumors, a mixed type (myxoid and round cell) liposarcoma, was t(12;16)(q13;p11), a rearrangement previously reported to be associated with myxoid liposarcoma. The other tumor, a pleomorphic liposarcoma, displayed massive numerical rearrangements (modal chromosome number 94-112), and numerous, mostly unidentifiable, marker chromosomes. The following clonal structural aberrations were recognized: del(1)(p22), del(1)(q23), t(7;?)(p22;?), i(17q), and t(19;?)(q13;?). 相似文献