Biopolym. Cell. 1991; 7(3):5-12.
Изучение молекулярных основ патологии на модели трансгенных животных
1Тарантул В. З., 1Мудрик Н. Н.
  1. Институт молекулярной генетики АН СССР
    Москва, СССР

Abstract

Рассматриваются эксперименты по трансгенозу, в результате которых на лабораторных животных (мыши, крысы) удалось смоделировать отдельные аномалии развития и различные патологии, встречающиеся у человека (рак, сахарный диабет, гипертензия, синдром Дауна). Исследования, проведенные на трансгенных животных, позволили выяснить молекулярно-генетические аспекты некоторых заболеваний.

References

[1] Alexander WS, Schrader JW, Adams JM. Expression of the c-myc oncogene under control of an immunoglobulin enhancer in E mu-myc transgenic mice. Mol Cell Biol. 1987;7(4):1436-44.
[2] Leder A, Pattengale PK, Kuo A, Stewart TA, Leder P. Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell. 1986;45(4):485-95.
[3] Koike K, Hinrichs SH, Isselbacher KJ, Jay G. Transgenic mouse model for human gastric carcinoma. Proc Natl Acad Sci U S A. 1989;86(14):5615-9.
[4] Ruther U, Garber C, Komitowski D, Muller R, Wagner EF. Deregulated c-fos expression interferes with normal bone development in transgenic mice. Nature. 1987 Jan 29-Feb 4;325(6103):412-6.
[5] Van Dyke TA, Finlay C, Miller D, Marks J, Lozano G, Levine AJ. Relationship between simian virus 40 large tumor antigen expression and tumor formation in transgenic mice. J Virol. 1987;61(6):2029-32.
[6] Hanahan D. Transgenic mice as probes into complex systems. Science. 1989;246(4935):1265-75.
[7] Lindgren V, Sippola-Thiele M, Skowronski J, Wetzel E, Howley PM, Hanahan D. Specific chromosomal abnormalities characterize fibrosarcomas of bovine papillomavirus type 1 transgenic mice. Proc Natl Acad Sci U S A. 1989;86(13):5025-9.
[8] Teitelman G, Alpert S, Hanahan D. Proliferation, senescence, and neoplastic progression of beta cells in hyperplasic pancreatic islets. Cell. 1988;52(1):97-105.
[9] Folkman J, Watson K, Ingber D, Hanahan D. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature. 1989;339(6219):58-61.
[10] Breuer M, Slebos R, Verbeek S, van Lohuizen M, Wientjens E, Berns A. Very high frequency of lymphoma induction by a chemical carcinogen in pim-1 transgenic mice. Nature. 1989;340(6228):61-3.
[11] Lavigueur A, Maltby V, Mock D, Rossant J, Pawson T, Bernstein A. High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene. Mol Cell Biol. 1989;9(9):3982-91.
[12] Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J. Acute leukaemia in bcr/abl transgenic mice. Nature. 1990;344(6263):251-3.
[13] Hinrichs SH, Nerenberg M, Reynolds RK, Khoury G, Jay G. A transgenic mouse model for human neurofibromatosis. Science. 1987;237(4820):1340-3.
[14] Nerenberg M, Hinrichs SH, Reynolds RK, Khoury G, Jay G. The tat gene of human T-lymphotropic virus type 1 induces mesenchymal tumors in transgenic mice. Science. 1987;237(4820):1324-9.
[15] Furuta Y, Aizawa S, Suda Y, Ikawa Y, Kishimoto H, Asano Y, Tada T, Hikikoshi A, Yoshida M, Seiki M. Thymic atrophy characteristic in transgenic mice that harbor pX genes of human T-cell leukemia virus type I. J Virol. 1989;63(7):3185-9.
[16] Green JE, Begley CG, Wagner DK, Waldmann TA, Jay G. trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene. Mol Cell Biol. 1989;9(11):4731-7.
[17] Epstein ChJ. The consequences of chromosomal imbalance: principles, mechanisms, models. New York: Cembridge Univ. press. 1986. 203 p.
[18] Epstein CJ, Avraham KB, Lovett M, Smith S, Elroy-Stein O, Rotman G, Bry C, Groner Y. Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome. Proc Natl Acad Sci U S A. 1987;84(22):8044-8.
[19] Schickler M, Knobler H, Avraham KB, Elroy-Stein O, Groner Y. Diminished serotonin uptake in platelets of transgenic mice with increased Cu/Zn-superoxide dismutase activity. EMBO J. 1989;8(5):1385-92.
[20] Bucchini D, Ripoche MA, Stinnakre MG, Desbois P, Lores P, Monthioux E, Absil J, Lepesant JA, Pictet R, Jami J. Pancreatic expression of human insulin gene in transgenic mice. Proc Natl Acad Sci U S A. 1986;83(8):2511-5.
[21] Selden RF, Skoskiewicz MJ, Howie KB, Russell PS, Goodman HM. Regulation of human insulin gene expression in transgenic mice. Nature. 1986 May 29-Jun 4;321(6069):525-8.
[22] Marban SL, DeLoia JA, Gearhart JD. Hyperinsulinemia in transgenic mice carrying multiple copies of the human insulin gene. Dev Genet. 1989;10(5):356-64.
[23] Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. 1985;313(6):353-60.
[24] Lo D, Burkly LC, Widera G, Cowing C, Flavell RA, Palmiter RD, Brinster RL. Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells. Cell. 1988;53(1):159-68.
[25] Sarvetnick N, Liggitt D, Pitts SL, Hansen SE, Stewart TA. Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma. Cell. 1988;52(5):773-82.
[26] Allison J, Campbell IL, Morahan G, Mandel TE, Harrison LC, Miller JF. Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic beta cells. Nature. 1988;333(6173):529-33.
[27] Bohme J, Haskins K, Stecha P, van Ewijk W, LeMeur M, Gerlinger P, Benoist C, Mathis D. Transgenic mice with I-A on islet cells are normoglycemic but immunologically intolerant. Science. 1989;244(4909):1179-83.
[28] Epstein PN, Overbeek PA, Means AR. Calmodulin-induced early-onset diabetes in transgenic mice. Cell. 1989;58(6):1067-73.
[29] Ham A, Cormac D. Histology. M. Mir, 1983. vol. 5:108-119.
[30] Ignatieva T. V., Golinsky G. F. Transgenic rats expressing human growth hormone gene as a model of some types of diabetes. Biopolym Cell. 1990; 6(2):24-31.
[31] Mullins JJ, Sigmund CD, Kane-Haas C, Gross KW, McGowan RA. Expression of the DBA/2J Ren-2 gene in the adrenal gland of transgenic mice. EMBO J. 1989;8(13):4065-72.
[32] Mullins JJ, Peters J, Ganten D. Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature. 1990;344(6266):541-4.
[33] Clouston WM, Lyons IG, Richards RI. Tissue-specific and hormonal regulation of angiotensinogen minigenes in transgenic mice. EMBO J. 1989;8(11):3337-43.
[34] Semenza GL, Traystman MD, Gearhart JD, Antonarakis SE. Polycythemia in transgenic mice expressing the human erythropoietin gene. Proc Natl Acad Sci U S A. 1989;86(7):2301-5.
[35] Lang RA, Metcalf D, Cuthbertson RA, Lyons I, Stanley E, Kelso A, Kannourakis G, Williamson DJ, Klintworth GK, Gonda TJ, et al. Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage. Cell. 1987;51(4):675-86.
[36] Cuthbertson RA, Lang RA. Developmental ocular disease in GM-CSF transgenic mice is mediated by autostimulated macrophages. Dev Biol. 1989;134(1):119-29.
[37] Stacey A, Bateman J, Choi T, Mascara T, Cole W, Jaenisch R. Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha 1(I) collagen gene. Nature. 1988;332(6160):131-6.
[38] Kuehn MR, Bradley A, Robertson EJ, Evans MJ. A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature. 1987 Mar 19-25;326(6110):295-8.
[39] Dycaico MJ, Grant SG, Felts K, Nichols WS, Geller SA, Hager JH, Pollard AJ, Kohler SW, Short HP, Jirik FR, et al. Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model. Science. 1988;242(4884):1409-12.
[40] Breitman ML, Clapoff S, Rossant J, Tsui LC, Glode LM, Maxwell IH, Bernstein A. Genetic ablation: targeted expression of a toxin gene causes microphthalmia in transgenic mice. Science. 1987;238(4833):1563-5.
[41] Evans GA. Dissecting mouse development with toxigenics. Genes Dev. 1989;3(3):259-63.
[42] Borrelli E, Heyman RA, Arias C, Sawchenko PE, Evans RM. Transgenic mice with inducible dwarfism. Nature. 1989;339(6225):538-41.
[43] Wolgemuth DJ, Behringer RR, Mostoller MP, Brinster RL, Palmiter RD. Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development. Nature. 1989;337(6206):464-7.
[44] Balling R, Mutter G, Gruss P, Kessel M. Craniofacial abnormalities induced by ectopic expression of the homeobox gene Hox-1.1 in transgenic mice. Cell. 1989;58(2):337-47.