[Study of the effect of the cDNA for the human apolipoprotein A-I gene in transgenic rabbits: modeling the neurological syndrome of human Tangier disease].
Two transgenic rabbits which carried human apolipoprotein A-1 (apo A-1) cDNA under mouse ribosomal protein L/32 promoter were obtained. The effectiveness of transgenosis was confirmed by DNA dot/blot and Southern blot hybridizations. Both transgenic animals had paralyses of fore or fore and high limbs. Electron microscopy demonstrated distinct degradative changes of those parts of spinal cord which were responsible for leg skeletal muscle innervation. RNA dot/blot hybridization showed transgene expression in liver and brain but not in kidney of adult transgenic animal. However, analysis of blood serum lipids and immunochemical determinations gave no indications of the presence of human apo A-1 in adult transgenic rabbit. The data obtained allow us to suggest that the observed pathology was due to interference of native and foreign protein products of apo A-1 gene expression in CNS in the course of embryo development. This suggestion was supported by results of in situ hybridization of 5- and 9-week human embryo sections with apo A-1 cDNA, showing effective expression of apo A-1 gene in neural cells of CNS. Results of transgenosis may be viewed as modeling of the neurological syndrome of human Tangier disease.
Perevozchikov
A P
AP
Vaĭsman
B L
BL
Sorokin
A V
AV
Kuryshev
V Iu
VIu
Vorob'ev
E V
EV
Dozortsev
D I
DI
Konovalov
G V
GV
Otellin
V A
VA
Dizhe
E B
EB
Missiul'
B V
BV
D000818:Animals; D030801:Animals, Genetically Modified; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004247:DNA; D006801:Humans; D008854:Microscopy, Electron; D008959:Models, Neurological; D009132:Muscles / Q000294:innervation / Q000378:metabolism / Q000648:ultrastructure; D009422:Nervous System Diseases / Q000150:complications / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011401:Promoter Regions, Genetic; D011817:Rabbits; D013631:Tangier Disease / Q000150:complications / Q000235:genetics*; D014018:Tissue Distribution
D016632:Apolipoprotein A-I; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase
Issledovanie na transgennykh krolikakh deĭstviia kDNK gena apolipoproteid A-I cheloveka: modelirovanie neĭrologicheskogo sindroma tenzhirskoĭ bolezni cheloveka.