Evaluación: Los alumnos seleccionarán 1 publicación de esta lista (o otra, relacionada con estos temas, previa consulta con el coordinador o el/la ponente correspondiente) para su presentación pública de forma MUY sucinta y esquemática (MÁXIMO 4 TRANSPARENCIAS) durante un máximo de 10 minutos. Durante la 2ª y 3ª semana del curso los alumnos se pondrán en contacto con los coordinadores del curso para acordar y organizar el orden de presentación de las publicaciones y evitar exposiciones duplicadas.

TEMA 1 - Transferencia génica en células. Origenes, situación actual y perspectivas. (Juan Ortín)

1.- Shortle D. and Nathans D. 1978. Local mutagenesis: a method for generating viral mutants with base substitutions in preselected regions of the viral genome.Proc Natl Acad Sci U S A 75:5 2170-2174.

2.- Graham F.L. and van der Eb, A.J. 1973. Transformation of rat cells by DNA of human adenovirus 5. Virology 54: 536-539.

3.- Perucho, M., Hanahan, D., Lipsich, L. and Wigler, M. 1980. Isolation of the chicken thymidine kinase gene by plasmid rescue. Nature 285: 207-210

4.- Fender et al. (1997). Adenovirus dodecahedron, a new vector for human gene transfer. Nature Biotech. 15, 52-56.

TEMA 2 - Transferencia génica mediante Adenovirus, Adeno-asociados y HSV. (José F. Rodríguez)

1.- Robbins, P. D., Tahara, H. and Ghivizzani, S.C. 1998. Viral vectors for gene therapy. TIBTECH  16, 35-40

2.- Yeh, P. and Perricaudet, M. 1997. Advances in adenoviral vectors: from genetic engineering to their biology. FASEB Journal 11,615-623.

3.- Verma, Y.M. and Somia, N. 1997. Gene therapy-promises, problems and prospects. Nature. 389, 239-242.

4.- Murphy, C. Y. et al. Expression of proteins in insect cells using baculovirus vectors. 1997.  In Current Protocols in Molecular Biology. John Wiley and Sons, Inc. pp 16.9.1-16.9.10.

5.- O’Reilly, D.R. , Miller, L.K. and Luckow, V.A. 1992. Baculovirus expression vectors. W.H. Freeman, New York.

TEMA 3 - Transferencia génica mediante vectores retrovirales. (Antonio Talavera)

1.- Coffin JM, Hughes SH and Varmus HE. (Eds.). (1998) Retroviruses. Cold Spring Harbor Laboratory Press.

2.- Vile R. (1991) The retroviral life cycle and the molecular construction of retrovirus vectors. En. "Practical Molecular Virology" (MKL Collins, ed.) Cap 1, pp 1-15.

3.- Talavera, A Martin F y Sánchez H.(1996). Los virus en la terapia génica. Publicación Oficial de la Sociedad Española de Virología:4:3-15.

4.- Guidotti JE et al. (1998). Retrovirus-mediated enzymatic correction of Tay-Sachs defect in transduced and nontransduced cells. Hum. Mol. Gen. 7:831-838.

5.- Talavera A, Liras A, Fuentes L  y Sánchez H.(2000). El VIH y otros retrovirus complejos en la terapia génica de células en reposo. Virología 7: 2-15.

TEMA 4 - Vectores no virales. Cromosomas artificiales. (Patricia Giraldo)

1.- Rols et al.  (1998) In vivo electrically mediated protein and gene transfer in murine melanoma. Nature Biotechnology 16: 168- 171.

2.- Lydiatt A, O’Sullivan DA (1998) Biochemical recovery and purification of gene therapy vectors. Curr. Opin. Biotechnol. 9(2): 177-185.

3.- Lasic D.D. (1998) Novel applications of liposomes. Trends in Biotechnology 16: 307-321.

4.- Huxley C. (1997) Mammalian artificial chromosomes and chromosome transgenics. Trends in Genetics 13(9): 345-347.

5.- Grimes BR, Schindelhauer D, McGill NI, Ross A, Ebersole TA, Cooke HJ. (2001) Stable gene expression from a mammalian artificial chromosome. EMBO Rep Oct;2(10):910-4

6.- Brown WR, Mee PJ, Hong Shen M. (2000) Artificial chromosomes: ideal vectors?. Trends Biotechnol. May;18(5):218-23.

7.- Jean-Michel H Vos (1998) Mammalian artificial chromosomes as tools for gene therapy. Current Opinion Genetics & Development 8:351-359.
 

TEMA 5 - Transferencia génica inducible: regulacion hormonal, regulacion por segundos mensajeros.  (Koldo Aurrekoetxea)

1.- Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, Vadlamudi RK, Kumar R. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol. 2001 Jan;3(1):30-7.

2.- Reichardt HM, Kaestner KH, Tuckermann J, Kretz O, Wessely O, Bock R, Gass P, Schmid W, Herrlich P, Angel P, Schutz G. DNA binding of the glucocorticoid receptor is not essential for survival. Cell. 1998 May 15;93(4):531-41.

3.- Shang Y, Myers M, Brown M. Formation of the androgen receptor transcription complex. Mol Cell. 2002 Mar;9(3):601-10.

4.- Darimont BD, Wagner RL, Apriletti JW, Stallcup MR, Kushner PJ, Baxter JD, Fletterick RJ, Yamamoto KR. Structure and specificity of nuclear receptor-coactivator interactions. Genes Dev. 1998 Nov 1;12(21):3343-56.

5.- Impey S, Fong AL, Wang Y, Cardinaux JR, Fass DM, Obrietan K, Wayman GA, Storm DR, Soderling TR, Goodman RH. Phosphorylation of CBP Mediates Transcriptional Activation by Neural Activity and CaM Kinase IV. Neuron. 2002 Apr 11;34(2):235-44.

6.- Bi K, Tanaka Y, Coudronniere N, Sugie K, Hong S, van Stipdonk MJ, Altman A. Antigen-induced translocation of PKC-theta to membrane rafts is required for T cell activation. Nat Immunol. 2001 Jun;2(6):556-63.

TEMA 6 - Transferencia génica específica de tejido. (José Ramón Naranjo)

1.- Aird WC, Edelberg JM, Weiler-Guettler H, Simmons WW, Smith TW, Rosenberg RD. Vascular bed-specific expression of an endothelial cell gene is programmed by the tissue microenvironment. J Cell Biol. 1997 Sep 8;138(5):1117-24.

2.- Tsien JZ, Chen DF, Gerber D, Tom C, Mercer EH, Anderson DJ, Mayford M, Kandel ER, Tonegawa S. Subregion- and cell type-restricted gene knockout in mouse brain. Cell. 1996 Dec 27;87(7):1317-26.

3.- Jones FS, Meech R. Knockout of REST/NRSF shows that the protein is a potent repressor of neuronally expressed genes in non-neural tissues. Bioessays. 1999 May;21(5):372-6.

4.- Mayford M, Baranes D, Podsypanina K, Kandel ER. The 3'-untranslated region of CaMKII alpha is a cis-acting signal for the localization and translation of mRNA in dendrites. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13250-5.

5.- Sassone-Corsi P. Goals for signal transduction pathways: linking up with transcriptional regulation. EMBO J. 1994 Oct 17;13(20):4717-28.

6.- Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000 Jan 6;403(6765):41-5.

7.- Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, Rosenfeld MG. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature. 1997 Jun 12;387(6634):677-84.

8.- Montminy M. Transcriptional activation. Something new to hang your HAT on. Nature. 1997 Jun 12;387(6634):654-5.

TEMA 7 - Animales transgénicos I (sobreexpresión, complementación génica) (Lluís Montoliu)

1.- Palmiter R.D, Brinster R.L. (1986) Germ-line transformation of mice. Ann. Rev. Genet. 20: 465-499.

2.- Pinkert CA (1997) The history and theory of transgenic animals. Lab. Animal. (September) 29-34.

3.- Montoliu L. et al. (1996) A locus control region at ?12 kb of the tyrosinase gene. The EMBO J. 15: 6026-6034.

4.- Peterson K.R. et al. (1997) Production of transgenic mice with yeast artificial chromosomes. Trends in Genetics 13: 61- 66.

5.- Bedell M. et al. (1997) Mouse models of human disease. Part I & II. Genes & Development. 11: 1-10, 11-43.

6.- Smith D.J. et al. (1997) Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome. Nature Genetics 16: 28-36.

7.- Mendez M.J. et al. (1997) Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice. Nature Genetics 15: 146-156.

8.- Bell AC, Felsenfeld G (1999) Stopped at the border: boundaries and insulators. Curr. Op. Gen & Develop. 9: 191-198.

9.- Li Q, Harju S, Peterson KR. Locus control regions: coming of age at a decade plus. Trends Genet. 1999 Oct;15(10):403-8.

10.- P Giraldo, L Montoliu (2001) Size matters: use of YACs, BACs and PACs in transgenic animals. Transgenic Research (2001). 10 (en prensa). Se facilitarán copias a los alumnos interesados

TEMA 8 - Animales transgénicos II (suicidas, indicadores e inducibles). (Lluís Montoliu)

1.- Borrelli E, Heyman R, Hsi M, Evans RM. Targeting of an inducible toxic phenotype in animal cells. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7572-6.

2.- Evans G.A. (1989) Dissecting mouse development with toxigenics. Genes & Development 3: 259-263.

3.- Salomon B, Lores P, Pioche C, Racz P, Jami J, Klatzmann D. Conditional ablation of dendritic cells in transgenic mice. J Immunol. 1994 Jan 15;152(2):537-48.

4.- Cohen JL, Boyer O, Salomon B, Onclerco R, Depetris D, Lejeune L, Dubus-Bonnet V, Bruel S, Charlotte F, Mattei MG, Klatzmann D. Fertile homozygous transgenic mice expressing a functional truncated herpes simplex thymidine kinase delta TKgene. Transgenic Res. 1998 Sep;7(5):321-30.

5.- Kistner A. et al. (1996) Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc. Natl. Acad. Sci. USA 93: 10933-10938.

6.- No D. et al. (1996) Ecdysone-inducible gene expression in mammalian cell and transgenic mice.
Proc. Natl. Acad. Sci.USA. 93: 3346-3351.

7.- Wang Y. et al. (1997) Ligand-inducible and liver target gene expression in transgenic mice. Nature Biotechnology 15: 239-243.

8.- Wells KD, Foster JA, Moore K, Pursel VG, Wall RJ. Codon optimization, genetic insulation, and an rtTA reporter improve performance of the tetracycline switch. Transgenic Res. 1999 Oct;8(5):371-81.

9.- Chin L, Tam A, Pomerantz J, Wong M, Holash J, Bardeesy N, Shen Q, O'Hagan R, Pantginis J, Zhou H, Horner JW 2nd, Cordon-Cardo C, Yancopoulos GD, DePinho RA. Essential role for oncogenic Ras in tumour maintenance. Nature. 1999 Jul 29;400(6743):468-72.

10.- Soulier S, Stinnakre MG, Lepourry L, Mercier JC, Vilotte JL. Use of doxycycline-controlled gene expression to reversibly alter milk-protein composition in transgenic mice. Eur J Biochem. 1999 Mar;260(2):533-9.
 

TEMA 9 - Transferencia génica y transferencia nuclear. Animales clónicos y transgénicos. (Lluís Montoliu)

1.- Gurdon JB. Nuclear transplantation in eggs and oocytes. J Cell Sci Suppl. 1986;4:287-318.

2.- McGrath J, Solter D. Nuclear transplantation in the mouse embryo by microsurgery and cell fusion. Science. 1983 Jun 17;220(4603):1300-2.

3.- Campbell KH, McWhir J, Ritchie WA, Wilmut I. Sheep cloned by nuclear transfer from a cultured cell line.  Nature. 1996 Mar 7;380(6569):64-6.

4.- Wilmut I. et al. (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810-813.

5.- Solter D. (1998) Dolly is a clone and no longer alone. Nature 394: 315-316.

6.- Campbell KHS (1999) Nuclear equivalence, nuclear transfer and the cell cycle. Cloning 1: 3-15.

7.- Wakayama T. et al. (1998) Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394: 369-374.

8.- Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce de Leon FA, Robl JM. Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science. 1998 May 22;280(5367):1256-8.

9.- Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, Yasue H, Tsunoda Y. Eight calves cloned from somatic cells of a single adult. Science. 1998 Dec 11;282(5396):2095-8.

10.- Kwon OY, Kono T. Production of identical sextuplet mice by transferring metaphase nuclei from four-cell embryos. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13010-3.

11.-Shiels PG, Kind AJ, Campbell KH, Waddington D, Wilmut I, Colman A, Schnieke AE. Analysis of telomere lengths in cloned sheep.  Nature. 1999 May 27;399(6734):316-7.

12.- Chan AW, Dominko T, Luetjens CM, Neuber E, Martinovich C, Hewitson L, Simerly CR, Schatten GP. Clonal propagation of primate offspring by embryo splitting. Science. 2000 Jan 14;287(5451):317-9.

13.- Polejaeva IA, Chen SH, Vaught TD, Page RL, Mullins J, Ball S, Dai Y, Boone J, Walker S, Ayares DL, Colman A, Campbell KH. Cloned pigs produced by nuclear transfer from adult somatic cells.Nature. 2000 Sep 7;407(6800):86-90.

14.- McCreath KJ, Howcroft J, Campbell KH, Colman A, Schnieke AE, Kind AJ. Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature. 2000 Jun 29;405(6790):1066-9.

15.- Colman A, Kind A. Therapeutic cloning: concepts and practicalities. Trends Biotechnol. 2000 May;18(5):192-6.

16.- Chan AWS, Chong KY, Martinovich C, Simerly C, Schatten G (2001)Transgenic monkeys produced by retroviral gene transfer into mature oocytes. Science 291: 309-312.

17.- Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG, Carolan C, Broadbent PJ, Robinson JJ, Wilmut I, Sinclair KD. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet. 2001 Feb;27(2):153-154.
 

TEMA 11 - Animales transgénicos en biotecnología. (Alfonso Gutiérrez-Adán)

1.- Jost B., Vilotte J.-L., Duluc I., Rodeau J-L., Freund J.-N., Production of low-lactose milk by ectopic expression of intestinal lactase in the mouse mammary gland. Nature Biotechnology 17 (1999) 160-164.

2.- Kerr D.E., Liang F., Bondioli K.R., Zhao H., Kreibich G., Wall R. J., Sun T., Liang F.X., Zhao H.P., Sun T.T., The bladder as a bioreactor: urothelium production and secretion of growth hormone into urine. Nature Biotechnology 16 (1998) 75-79.

3.- Schnieke A.E., Kind A.J., Ritchie W.A., Mycock K., Scott A.R., Ritchie M., Wilmut I., Colman A., Campbell K.H., Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278 (1997) 2130-2133.

4. Harvey, A. J., Speksnijder, G., Baugh, L. R., Morris, J. A. & Ivarie, R. Expression of exogenous protein in the egg white of transgenic chickens. Nat Biotechnol 20, 396-9. (2002).

5. Pintado, B. & Gutierrez-Adan, A. Transgenesis in large domestic species: future development for milk modification. Reprod Nutr Dev 39, 535-44. (1999).
 

TEMA 12 - Animales transgénicos en el estudio de encefalopatías transmisibles. (Belén Pintado)

1.- Bueler H, Aguzzi A, Sailer A, Greiner RA, Autenried P, Aguet M, Weissmann C. Mice devoid of PrP are resistant to scrapie. Cell 1993; 73: 1339-1347.

2.- Hill, A.F., Joiner, S., Linehan, J., Desbruslais, M., Lantos, P. Collinge, J. ,2000. Species-barrier-independent prion replication in apparently resistant species. Proc. Nat. Acad. Sci. USA 97: 10248-10253.

3.- Scott MR, Safar J, Telling G, Nguyen O, Groth D, Torchia M, Koehler R, Tremblay P, Walther D, Cohen FE, DeArmond SJ, Prusiner SB. Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice. Proc Natl Acad Sci U S A 1997; 94: 14279-14284.

4.- Raeber AJ, Brandner S, Klein MA, Benninger Y, Musahl C, Frigg R, Roeckl C, Fischer MB, Weissmann C, Aguzzi A. Transgenic and knockout mice in research on prion diseases. Brain Pathol 1998; 8: 715-733.

5.- Heppner FL, Musahl C, Arrighi I, Klein MA, Rulicke T, Oesch B, Zinkernagel RM, Kalinke U, Aguzzi A. Prevention of scrapie pathogenesis by transgenic expression of anti- prion protein antibodies. Science 2001; 294: 178-182.
 

TEMA 13 - Transferencia genética mediada por células germinales. (Pedro Esponda)

1.- Huguet E, Esponda P (1998) Foreign DNA introduced into the vas deferens is gained by mammalian spermatozoa. Molecular Reproduction and Development. 51: 42-52.

2.- Perry ACF, Wakayama T, Kishikawa H, Kasai T, Okabe M, Toyoda Y, Yanagimachi R (1998) Mammalian transgenesis by intracitoplasmatic Sperm Injection. Science 284: 1180-1183.

3.- Spadafora C (1998) Sperm cells and foreign DNA: a controversial relation. BioEssays 20: 955-964.

TEMA 14 - Animales transgénicos con expresión inducible en el estudio de enfermedades neurodegenerativas. (José J. Lucas)

1.- Keltz MB, Chen J, Carlezon WA Jr, Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L,

2.- Self DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ. (1999) "Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine."  Nature 401(6750): 272-276.

3.- Gingrich JR, Roder J. (1998) "Inducible gene expression in the nervous system of transgenic mice" Annu. Rev. Neurosci. 21: 377-405.

4.- Mayford M, Mansui M, Muller R, Kandel ER (1997) "Memory and behavior: a second generation of genetically modified mice." Current Biology 7: 580-589

5.- Lucas, J.J., Hernández, F, Gómez-Ramos P., Morán M.A., Hen R., and Avila J. (2001) Decreased nuclear ß-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3ß conditional transgenic mice. EMBO J. 20: 27-39.

6.- Yamamoto, A., Lucas, J.J., and Hen, R. (2000) Reversal of neuropathology and motor dysfunction in a conditional model of Huntingtron´s Disease. Cell  101: 57-66.
Ver también:Minireview por Orr, H.T. and Zoghbi, H.Y. en Cell 101:1-4
 News and Views por Bates, G. en Nature 404: 944-945

7.- Mansuy IM and Bujard H (2000) "Tetracycline-regulated gene expression in the brain." Current Opinion in Neurobiology 10: 593-596.

TEMA 15 - Células embrionales totipotentes (ES). (Miguel Torres)

1.- Evans MJ and Kaufman MH. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154-156.

2.- Robertson EJ. (1986). Pluripotential stem cell lines as a route into the mouse germ line. Trends. Genet 2: 9-13.

3.- Fedorov LM , Haegel-Kronenberger H & Hirchenhain J. (1997).  A comparison of the germline potential of differently aged ES cell lines and their transfected descendants. Transgenic Research 6: 223-231.

4.- Udy GB, Parkes BD & Wells DN. (1997). ES cell cycle rates affect gene targeting frequencies . Exp. Cell Res 231: 296-301.

5.- Brook FA & Gardner RL. (1997).The origin and efficient derivation of embryonic stem cells in the mouse.  Proc. Natl. Acad. Sci. USA 94: 5709-5712.

6.- Dani C, Chambers I et al. (1998). Paracrine induction of stem cell renewal by LIF-deficient cells: a new ES cell regulatory pathway. Dev. Biol. 203:149-162.

7.- Nichols J, Zevnik B et al. (1998). Formation of pluripotent stem cells in the mammalian embryo depends on the POU Transcription Factor Oct4. Cell 95:379-391

8.- Shamblott MJ, Axelman J et al. (1998) Derivation of pluripotent stem cells from cultures human primordial germ cells. 95:13726-13731.

9- Thomson JA, Itskovitz-Eldor J et al. (1998) Embryonic stem cells derived from human blastocysts. Science  282: 1145-1147.

10- Raz R, Lee CK et al. (1999) Essential role of STAT3·for embryonic stem cell pluripotency. Proc. Natl. Acad. Sci. USA 96:2846-2851.

11- Thomson JA and Odorico JS. (2000) Human embryonic stem cells and embryonic germ cell lines. TIBTECH 18: 53-57

12- Amit A, Carpenter MK, Inokuma MS et al. (2000) Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev. Biol 227:271-278.

TEMA 16 - Diferenciación de células ES. Aplicaciones biomédicas. (Lluís Montoliu)

1.- Keller GM.  In vitro differentiation of embryonic stem cells. Curr. Op. In Cell Biol. (1995) 7: 862-869.

2.- Brüstle O, Jones KN,  Learish RD et al. Embryonic stem-cell-derived glial precursors: a source of myelinating transplants. Science (1999). 285: 754-756.

3.- Bjornson CRR, Rietze RL, Reynolds BA et al. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science (1999) 283: 534-537.

4.- Mezey E, Chandross K et al. Turning blood into brain: cells bearing neuronal antigens generated in vivo fron bone marrow. Science (2000): 290:1779-1782.

5.- Fairchild PJ, Brook FA, Gardner et al. Directed differentiation of dendritic cells  from mouse embryonic stem cells. Current Biol. (2000) 10:1515-1518.

6.- Schuldiner M, Yanuka O et al. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. PNAS (2000) 97 (21) 11307-11312.

7.- Munsie MJ, Michalska AE et al. Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Current Biol (2000) 10:989-992

8.- Liu S. Qu Y et al. Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture after spinal cord transplantation. PNAS (2000) 97(11) 6126-6131

9.- Reubinoff BE, Pera MF et al Embryonic stem cells lines from human blastocysts: somatic differentiation in vitro.  Nature Biotechnolgy (2000) 18: 399-404

10.- Shamblott MJ, Axelman J et al. Human embryonic germ cell derivatives express a broad range of developmentally distinct markers and proliferate extensively in vitro. PNAS (2001) 98 (1) 113-118.

TEMA 17 - Diferenciación in vitro de células madre. (Bernat Soria)

1.- Soria B, Roche E, Berna G, Leon-Quinto T, Reig JA, Martin F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes. 2000 Feb;49(2):157-62.

TEMA 19 - Manipulación genética de ratones I. Ratones “knock-out”. (Sagrario Ortega)

1.- Nature 1988 Nov 24;336(6197):348-52. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Mansour SL, Thomas KR, Capecchi MR

2.- Science 1989 Jun 16;244(4910):1288-92. Altering the genome by homologous recombination. Capecchi MR

3.- Proc Natl Acad Sci U S A 1990 Oct;87(19):7688-92. Introduction of a lacZ reporter gene into the mouse int-2 locus by homologous recombination.
Mansour SL, Thomas KR, Deng CX, Capecchi MR

4.- Nature 1990 Aug 30;346(6287):847-50. Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development.
Thomas KR, Capecchi MR

TEMA 20 - Manipulación genética de ratones II. Ratones “knock-in” y condicionales. (MªVictoria Campuzano)

TISSUE SPECIFIC MUTATIONS: THE CRE-LOXP SYSTEM

1.- Science 1994 Jul 1;265(5168):103-6. Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K

2.- Proc Natl Acad Sci U S A 1997 Dec 23;94(26):14602-7. Protamine-Cre recombinase transgenes efficiently recombine target sequences in the male germ line of mice, but not in embryonic stem cells. O'Gorman S, Dagenais NA, Qian M, Marchuk Y

3.- Cell 1999 Feb 5;96(3):329-39. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR

INDUCIBLE GENE TARGETING

4.- Science 1995 Sep 8;269(5229):1427-9. Inducible gene targeting in mice. Kuhn R, Schwenk F, Aguet M, Rajewsky K

5.- Proc Natl Acad Sci U S A 1995 Jul 18;92(15):6991-5. Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinas. Metzger D, Clifford J, Chiba H, Chambon P

6.- Proc Natl Acad Sci U S A 1997 Dec 23;94(26):14559-63. Spatio-temporally controlled site-specific somatic mutagenesis in the mouse. Brocard J, Warot X, Wendling O, Messaddeq N, Vonesch JL, Chambon P, Metzger D

7.- J Mol Biol 1999 Jan 8;285(1):175-82. Inducible site-specific recombination in the brain. Kellendonk C, Troche F, Casanova E, Anlag K, Opherk C, Schutz G

OTHER USES OF GENE TARGETING: Chromosome Engeneering

8.- Nature 1995 Dec 14;378(6558):720-4.Chromosome engineering in mice. Ramirez-Solis R, Liu P, Bradley A

9.- Methods 1997 Dec;13(4):423-36. Using targeted large deletions and high-efficiency N-ethyl-N-nitrosourea mutagenesis for functional analyses of the mammalian genome. Justice MJ, Zheng B, Woychik RP, Bradley A

TEMA 21 - Ratones knock-out y ciclo celular. (Marcos Malumbres)

1. Lee, E. Y. H. P. et al. Mice deficient for Rb are nonviable and show defects in neurogenesis and hematopoiesis. Nature 359, 288-294 (1992).

2. Jacks, T. et al. Effects of an Rb mutation in the mouse. Nature 359, 295-300 (1992).

3. Geng Y., Whoriskey W., Park M.Y., Bronson R.T., Medema R.H., Li T., Weinberg R.A., Sicinski P. (1999). Rescue of cyclin D1 deficiency by knockin cyclin E. Cell 97, 767-777.

4. Rane S.G., Dubus P., Mettus R.V., Galbreath E.J., Boden G., Reddy E.P., Barbacid M. (1999). Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in ß-islet cell hyperplasia. Nature Genetics 22, 44-52.

5. Sotillo, R. et al. Wide spectrum of tumors in knock in mice carrying a Cdk4 protein insensitive to INK4 inhibitors. EMBO J. 20, 6637-6647 (2001).

6. Malek, N. P. et al. A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase. Nature 413, 323-327 (2001).

7. Krimpenfort, P., Quon, K. C., Mooi, W. J., Loonstra, A. & Berns, A. Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice. Nature 413, 83-86 (2001).

8. Sharpless, N. E. et al. Loss of p16INK4a with retention of p19ARF predisposes to tumorigenesis. Nature 413, 86-91 (2001).

9. Dannenberg, J.-H., van Rossum, A., Schuijff, L. & te Riele, H. Ablation of the retinoblastoma gene family deregulates G1 control causing immortalization  and increased cell turnover under growth-restricting conditions. Genes Dev. 14, 3051-3064 (2000).

10. Sage, J. et al. Targeted disruption of the three Rb-related genes leads to loss of G1 control and immortalization. Genes Dev. 14, 3037-3050 (2000).

11. Yu, Q., Geng, Y. & Sicinski, P. Specific protection against breast cancers by cyclin D1 ablation. Nature 411, 1017-1021 (2001).

12. Michel, L. S. et al. MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 409, 355-359 (2001).

13. St. John, M. A. R. et al. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nature Genet. 21, 182-186 (1999).