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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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In a child with some features of Turner's syndrome, gonosomal mosaicism with an isodicentric nonfluorescent (idic)Y chromosome was detected (mos 45,X/47,X,idic(Y)(q11),idic(Y)(11)/46,X,idic(Y)(q11)). Histopathological examination showed streak gonads with some evidence of ovarian stroma and no sign of gonadoblastoma. Polymerase chain reaction (PCR) analysis in blood lymphocytes and gonadal tissues using primers of seven loci along the Y chromosome, including the sex determined region (SRY), azoospermia factor region (AZF) and the deleted in azoospermia ( DAZ ) gene was positive for all loci tested, confirming the isodicentric character of the Y chromosome and indicating the presence of the AZF region. It is remarkable that the existence of spermatogenesis controlling genes does not play an important role in gonadal development and differentiation in a phenotypic female with some Turner stigmata. The data presented here are briefly discussed with previously-described patients. 相似文献
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A chimeric protein containing most of the hepatitis B virus preS2 region (amino acid residues 1–48) upstream to, and colinear with the amino-terminus of bluetongue virus VP7 protein (preS2VP7) was expressed by a recombinant Autographa californica nuclear polyhedrosis virus (AcNPV). The chimeric protein formed BTV core-like particles (CLPs) in Spodoptera frugiperda cells only when the cells were coinfected with this recombinant virus and a recombinant baculovirus that expresses unmodified VP7 and VP3 of BTV. The ratio of preS2VP7 incorporated into CLPs was influenced by the relative multiplicities of infection of the two viruses. Immunoelectron microscopy of the chimeric particles indicated that the preS2 epitope was exposed on the surface of the CLPs. When insect cells were coinfected with the preS2 VP7 recombinant virus and a baculovirus vector that synthesized only the VP3 protein, no CLPs were identified. 相似文献
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Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection 相似文献
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