Knockin animal models of inherited arrhythmogenic diseases: What have we learned from them?

Journal of Cardiovascular Electrophysiology

Volumn 18, Issue 10, 2007, Pages 1117-1125

  Nilles, Kathy M ^a   London, Barry ^a,b  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

Arrhythmia; Gene targeting; Knockin; Mouse; Sudden death

Indexed keywords

ELECTROCARDIOGRAPHY; ELECTROPHYSIOLOGY; GENE EXPRESSION; GENETIC ENGINEERING; HEART ARRHYTHMIA; HEART MUSCLE CELL; HUMAN; KNOCKOUT GENE; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; DISEASE MODELS, ANIMAL; HEART DEFECTS, CONGENITAL; HUMANS; MICE; MICE, TRANSGENIC;

EID: 34548697504     PISSN: 10453873     EISSN: 15408167     Source Type: Journal    
DOI: 10.1111/j.1540-8167.2007.00884.x     Document Type: Review

References (81)

1. Koretsky AP : Investigation of cell physiology in the animal using transgenic technology. Am J Physiol 262 (Cell Physiol) 1992 31 : C261 C275.
2. Shastry BS : Gene disruption in mice: Models of development and disease. Mol Cell Biochem 1998 181 : 163 179.
3. Salama G, London B : Mouse models of long QT syndrome. J Physiol 2007 578 : 43 53.
4. London B : Mouse models of cardiac arrhythmias. Cardiac Electrophysiology: From Cell to Bedside. 4th ed. Philadelphia, PA : Saunders, 2004, pp. 433 443.
5. Charpentier F, Demolombe S, Escande D : Cardiac channelopathies: From mice to men. Ann Med 2004 36 : 28 34.
6. Huang WY, Aramburu J, Douglas PS, Izumo S : Transgenic expression of green fluorescence protein can cause dilated cardiomyopathy. Nat Med 2000 6 : 482 483.
7. Nerbonne JM, Nichols CG, Schwartz TL, Escande D : Genetic manipulation of cardiac K+ channel function in mice: what have we learned, and where do we go from here? Circ Res 2001 89 : 944 956.
8. Theis M, Magin TM, Plum A, Willecke K : General or cell type-specific deletion and replacement of connexin-coding DNA in the mouse. Methods 2000 20 : 205 218.
9. Liu K, Hipkens S, Yang T, Abraham R, Zhang W, Chopra N, Knollmann B, Magnuson MA, Roden DM : Recombinase-mediated cassette exchange to rapidly and efficiently generate mice with human cardiac sodium channels. Genesis 2006 44 : 556 564.
10. London B, Jeron A, Zhou J, Buckett P, Han X, Mitchell GF, Koren G : Long QT and ventricular arrhythmias in transgenic mice expressing the N-terminus and first transmembrane segment of a voltage-gated potassium channel. Proc Natl Acad Sci USA 1998 95 : 2926 2931.
11. Wang L, Duff HJ : Developmental changes in transient outward current in mouse ventricle. Circ Res 1997 81 : 120 127.
12. Knollman BC, Katchman AN, Franz MR : Monophasic action potential recordings from intact mouse heart: Validation, regional heterogeneity, and relation to refractoriness. J Cardiovasc Electrophysiol 2001 12 : 1286 1294.
13. Guerrero PA, Schuessler RB, Davis LM, Beyer EC, Johnson CM, Yamada KA, Saffitz JE : Slow ventricular conduction in mice heterozygous for a connexin43 null mutation. J Clin Invest 1997 99 : 1991 1998.
14. Morley GE, Vaidya D, Samie FH, Lo CW, Delmar M, Jalife J : Characterization of conduction in the ventricles of normal and heterozygous connexin43 knockout mice using optical mapping. J Cardiovasc Electrophysiol 1999 10 : 1361 1375.
15. Baker LC, London B, Choi B-R, Koren G, Salama G : Enhanced dispersion of repolarization and refractoriness in transgenic mouse hearts promotes reentrant ventricular tachycardia. Circ Res 2000 86 : 396 407.
16. London B, Baker LC, Lee JS, Shusterman V, Choi B-R, Kubota T, McTiernan CF, Feldman AM, Salama G : Calcium-dependent arrhythmias in transgenic mice with heart failure. Am J Physiol Heart Circ Physiol 2003, 284 : H431 441.
17. Tamaddon HS, Vaidya D, Simon AM, Paul DL, Jalife J, Morley GE : High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system. Circ Res 2000 87 : 929 936.
18. Rentschler S, Vaidya DM, Tamaddon H, Degenhardt K, Sassoon D, Morley GE, Jalife J, Fishman GI : Visualization and functional characterization of the developing murine cardiac conduction system. Development 2001 128 : 1785 1792.
19. London B : Cardiac arrhythmias: From (transgenic) mice to men. J Cardiovasc Electrophysiol 2001 12 : 1089 1091.
20. Gehrmann J, Hammer PE, Maguire CT, Wakimoto H, Triedman JK, Berul CI : Phenotypic screening for heart rate variability in the mouse. Am J Physiol Heart Circ Physiol 2000, 279 : H733 H740.
21. Shusterman V, Usiene I, Harrigal C, Lee JS, Kubota T, Feldman AM, London B : Strain-specific patterns of cardiac rhythm and autonomic nervous system activity in mice. Am J Physiol Heart Circ Physiol 2002, 282 : H2076 H2083.
22. Berul CI, Aronovitz MJ, Wang PJ, Mendelsohn ME : In vivo cardiac electrophysiology studies in the mouse. Circulation 1996 94 : 2461 2468.
23. VanderBrink BA, Sellitto C, Saba S, Link MS, Zhu W, Homoud MK, Estes NA 3rd., Paul DL, Wang PJ : Connexin40-deficient mice exhibit atrioventricular nodal and infra-Hisian conduction abnormalities. J Cardiovasc Electrophysiol 2000 11 : 1270 1276.
24. Gutstein DE, Danik SB, Sereysky JB, Morley GE, Fishman GI : Subdiaphragmatic murine electrophysiological studies: Sequential determination of ventricular refractoriness and arrhythmia induction. Am J Physiol Heart Circ Physiol 2003, 285 : H1091 H1096.
25. Trepanier-Boulay V, St-Michel C, Tremblay A, Fiset C : Gender-based differences in cardiac repolarization in mouse ventricle. Circ Res 2001 89 : 437 444.
26. Schwartz PJ : The congenital long QT syndromes from genotype to phenotype: clinical implications. J Intern Med 2006 259 : 39 47.
27. Vetter DE, Mann JR, Wangemann P, Liu J, McLaughlin KJ, Lesage F, Marcus DC, Lazdunski M, Heinemann SF, Barhanin J : Inner ear defects induced by null mutation of the isk gene. Neuron 1996 17 : 1251 1264.
28. Drici M-D, Arrighi I, Chouabe C, Mann JR, Lazdunski M, Romey G, Barhanin J : Involvement of IsK-associated K+ channel in heart rate control of repolarization in a murine engineered model of Jervell and Lange-Nielsen syndrome. Circ Res 1998 83 : 95 102.
29. Letts VA, Valenzuela A, Dunbar C, Zheng QY, Johnson KR, Frankel WN : A new spontaneous mouse mutation in the Kcne1 gene. Mamm Genome 2000 11 : 831 835.
30. Kupershmidt S, Yang T, Anderson ME, Wessels A, Niswender KD, Magnuson MA, Roden DM : Replacement by homologous recombination of the minK gene with lacZ reveals restriction of minK expression to the mouse cardiac conduction system. Circ Res 1998 84 : 146 152.
31. van Veen TAB, van Rijen HVM, Opthof T : Cardiac gap junction channels: modulation of expression and channel properties. Cardiovasc Res 2001 51 : 217 229.
32. Kreuzberg MM, Schrickel JW, Ghanem A, Kim J-S, Degen J, Janssen-Bienhold U, Lewalter T, Tiemann K, Willecke K : Connexin30.2 containing gap junction channels decelerate impulse propagation through the atrioventricular node. Proc Natl Acad Sci USA 2006 103 : 5959 5964.
33. Kruger O, Plum A, Kim JS, Winterhager E, Maxeiner S, Hallas G, Kirchoff S, Traub O, Lamers WH, Willecke K : Defective vascular development in connexin 45-deficient mice. Development 2000 127 : 4179 4193.
34. Kumai M, Nishii K, Nakamura K, Takeda N, Suzuki M, Shibata Y : Loss of connexin45 causes a cushion defect in early cardiogenesis. Development 2000 127 : 3501 3512.
35. Groenewegen WA, Firouzi M, Bezzina CR, Vliex S, van Langen IM, Sankjuijl L, Smits JPP, Hulsbeek M, Rook MB, Jongsma HB, Wilde AAM : A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill. Circ Res 2003 92 : 14 22.
36. Firhouzi M, Ramanna H, Kok B, Jongsma HB, Koeleman BPC, Doevendans PA, Groenewegen WA, Hauer RNW : Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation. Circ Res 2004 95 : e29-e33.
37. Juang JM, Chern YR, Tsai CT, Chiang FT, Lin JL, Hwang JJ, Hsu KL, Tseng CD, Tseng YZ, Lai LP : The association of human connexin 40 genetic polymorphisms with atrial fibrillation. Int J Cardiol 2007 116 : 107 112.
38. Reaume AG, de Sousa PA, Kulliarni S, Langille BL, Zhu D, Davies TC, Juneja SC, Kidder GM, Rossant J : Cardiac malformation in neonatal mice lacking connexin43. Science 1995 267 : 1831 1834.
39. Ya J, Erdtsiecke-Ernste EB, de Boer PA, van Kempen MJ, Jongsma H, Gros D, Moorman AF, Lamers WH : Heart defects in connexin43-deficient mice. Circ Res 1998 82 : 360 366.
40. Gutstein DE, Morley GE, Tamaddon H, Vaidya D, Schneider MD, Chen J, Chien KR, Stuhlmann H, Fishman GI : Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43. Circ Res 2001 88 : 333 339.
41. Elfgang C, Eckert R, Lichtenberg-Frate H, Butterweck A, Traub O, Klein RA, Hulser DF, Willecke K : Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. J Cell Biol 1995 129 : 805 817.
42. Zheng-Fischhofer Q, Ghanem A, Kim J-S, Kibschull M, Schwarz G, Schwab JO, Nagy J, Winterhager E, Tiemann K, Willecke K : Connexin31 cannot functionally replace connexin43 during cardiac morphogenesis in mice. J Cell Sci 2006 119 : 693 701.
43. Plum A, Hallas G, Magin T, Dombrowski F, Hagendorf A, Schumacher B, Wolpert C, Kim J-S, Lamers WH, Evert M, Meda P, Traub O, Willecke K : Unique and shared functions of different connexins in mice. Curr Biol 2000 10 : 1083 1091.
44. London B, Guo W, Pan X, Lee JS, Shusterman V, Rocco CJ, Logothetis DA, Nerbonne JM, Hill JA : Targeted replacement of Kv1.5 in the mouse leads to loss of the 4-aminopyridine-sensitive component of IK,slow and resistance to drug-induced QT prolongation. Circ Res 2001 88 : 940 946.
45. Bennett PB, Yazawa K, Makita N, George AL Jr. : Molecular mechanism for an inherited cardiac arrhythmia. Nature 1995 376 : 683 685.
46. Nuyens D, Stengl M, Dugarmaa S, Rossenbacker T, Compernolle V, Rudy Y, Smits JF, Flameng W, Clancy CE, Moons L, Vos MA, Dewerchin M, Benndorf K, Collen D, Carmeliet E, Carmeliet P : Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome. Nat. Med 2001 7 : 1021 1027.
47. Tateyama M, Kurokawa J, Terrenoire C, Rivolta I, Kass RS : Stimulation of protein kinase C inhibits bursting in disease-linked mutant human cardiac sodium channels. Circulation 2003 107 : 3216 3222.
48. Fabritz L, Kirchhof P, Franz MR, Nuyens D, Rossenbacker T, Ottenhof A, Haverkamp W, Breithardt G, Carmeliet E, Carmeliet P : Effect of pacing and mexilitine on dispersion of repolarisation and arrhythmias in ΔKPQ SCN5A (long QT3) mice. Cardiovasc Res 2003 57 : 1085 1093.
49. Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantu F, Towbin JA, Keating MT, Hammoude H, Brown AM, Chen LS : Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation 1995 92 : 3381 3386.
50. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G, Ortiz-Lopez R, Wang Z, Antzelevitch C, O'Brien R, Schulze-Bahr E, Keating MT, Towbin JA, Wang Q : Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998 392 : 293 296.
51. Schott J-J, Alshinawi C, Kyndt F, Probst V, Hoorntje TM, Hulsbeek M, Wilde AM, Escande D, Mannens M, Le Marec H : Cardiac conduction defects associate with mutations in SCN5A. Nat Genet 1999 23 : 20 21.
52. Papadatos GA, Wallerstein PMR, Head CEG, Ratcliff R, Brady PA, Benndorf K, Saumarez RC, Trezise AEO, Huang CL-H, Vandenberg JI, Colledge WH, Grace AA : Slowed conduction and ventricular tachycardia after targeted disruption of the targeted sodium channel gene Scn5a. Proc Natl Acad Sci USA 2002 99 : 6210 6215.
53. Royer A, van Veen TAB, Le Bouter S, Marionneau C, Griol-Charhbili V, Leoni A-L, Steenman M, van Rijen HVM, Demolombe S, Goddard CA, Richer C, Escoubet B, Jarry-Guichard T, Colledge WH, Gros D, de Bakker JMT, Grace AA, Escande D, Charpentier F : Mouse model of SCN5A-linked hereditary Lenegre's disease: age-related conduction slowing and myocardial fibrosis. Circulation 2005 111 : 1738 1746.
54. Bezzina C, Veldkamp M, Van Den Bert M, Postma A, Rook M, Viersma J, Van Langen I, Tan-Sindhunata G, Bink-Boelkens M, Van Der Hout A, Mannens M, Wilde A : A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res 1999 85 : 1206 1213.
55. Remme CA, Verkerk AO, Nuyens D, van Ginneken ACG, van Brunschot S, Belterman CNW, Wilders R, van Roon MA, Tan HL, Wilde AAM, Carmeliet P, de Bakker JMT, Veldkamp MW, Bezzina CR : Overlap syndrome of cardiac sodium channel disease in mice carrying the equivalent mutation of human SCN5A-1795insD. Circulation 2006 114 : 2584 2594.
56. Bers DM : Cardiac excitation-contraction coupling. Nature 2002 415 : 198 205.
57. Priori SG, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, Sorrentino V, Danieli GA : Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 2001 103 : 196 200.
58. Priori SG, Napolitano C, Memmi M, Colombi B, Drago F, Gasparini M, DeSimone L, Coltorti F, Bloise R, Keegan R, Cruz Filho FES, Vignati G, Benatar A, DeLogu A : Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002 106 : 69 74.
59. Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A : Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet 2001 10 : 189 194.
60. Danieli GA, Rampazzo A : Genetics of arrhythmogenic right ventricular cardiomyopathy. Curr Opin Cardiol 2002 17 : 218 221.
61. Jiang D, Xiao B, Zhang L, Chen SR : Enhanced basal activity of a cardiac Ca2 +channel release channel (ryanodine receptor) mutant associated with ventricular tachycardia and sudden death. Circ Res 2002 91 : 218 225.
62. Jiang D, Wang R, Xiao B, Kong H, Hunt DJ, Choi P, Zhang L, Chen SR : Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2 +activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden cardiac death. Circ Res 2005 97 : 1173 1181.
63. Cerrone M, Colombi B, Santoro M, di Barletta MR, Scelsi M, Villani L, Napolitano C, Priori SG : Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor. Circ Res 2005 96 : e77-e82.
64. Liu N, Colombi B, Memmi M, Zissimopoulos S, Rizzi N, Negri S, Imbriani M, Napolitano C, Lai FA, Priori SG : Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia: insights from a RyR2 R4496C knock-in mouse model. Circ Res 2006 99 : 292 298.
65. Wehrens XH, Lehnart SE, Huang F, Vest JA, Reiken SR, Mohler PJ, Sun J, Guatimosim S, Song LS, Rosemblit N, D'Armiento JM, Napolitano C, Memmi M, Prior SG, Lederer WJ, Marks AR : FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 2003 113 : 829 840.
66. Wehrens XH, Lehnart SE, Reiken SR, Deng SX, Vest JA, Cervantes D, Coromilas J, Landry DW, Marks AR : Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2. Science 2004 304 : 292 296.
67. Lehnart SE, Terrenoire C, Reiken S, Wehrens XHT, Long-Sheng S, Tillman EJ, Mancarella S, Coromilas J, Lederer WJ, Kass RS, Marks AR : Stabilization of cardiac ryanodine receptors prevents intracellular calcium leak and arrhythmias. Proc Natl Acad Sci USA 2006 103 : 7906 7910.
68. Bauce B, Rampazzo A, Basso C, Bagattin A, Daliento L, Tiso N, Turrini P, Thiene G, Danieli GA, Nava A : Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers. J Am Coll Cardiol 2002 40 : 341 349.
69. Thomas NL, George CH, Lai FA : Functional heterogeneity of ryanodine receptor mutations associated with sudden cardiac death. Cardiovasc Res 2004 64 : 52 60.
70. Thomas NL, Lai FA, George CH : Differential Ca2+ sensitivity of RyR2 mutations reveals distinct mechanisms of channel dysfunction in sudden cardiac death. Biochem Biophys Res Commun 2005 331 : 231 238.
71. Kannankeril PJ, Mitchell BM, Goonasekera SA, Chelu MG, Zhang W, Sood S, Kearney D, Danila CI, de Biasi M, Wehrens XHT, Pautler RG, Roden DM, Taffet GE, Dirksen RT, Anderson ME, Hamilton SL : Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy. Proc Natl Acad Sci USA 2006 103 : 12179 12184.
72. Nagy A : Cre recombinase: The universal reagent for genome tailoring. Genesis 2000 26 : 99 109.
73. Skvorak K, Vissel B, Homanics GE : Production of conditional point mutant knockin mice. Genesis 2006 44 : 345 353.
74. Bayascas JR, Sakamoto K, Armit L, Arthur JSC, Alessi DR : Evaluation of approaches to generation of tissue-specific knock-in mice. J Biol Chem 2006 281 : 28772 28781.
75. Stankunas K, Bayle JH, Gestwicki JE, Lin Y-M, Wandless TJ, Crabtree GR : Conditional protein alleles using knockin mice and a chemical inducer of dimerization. Mol Cell 2003 12 : 1615 1624.
76. Topaloglu O, Hurley PJ, Yildirim O, Civin CI, Bunz F : Improved methods for the generation of human gene knockout and knockin cell lines. Nucl Acids Res 2005 33 : e158.
77. Mohler PJ : Ankyrins and human disease: What the electrophysiologist should know. J Cardiovasc Electrophysiol 2006 17 : 1153 1159.
78. Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A, Napolitano C, Anumonwo J, di Barletta MR, Gudapakkam S, Bosi G, Stramba-Badiale M, Jalife J : A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 2005 96 : 800 807.
79. Alcolea S, Therese J-G, de Bakker J, Gonzalez D, Lamers W, Coppen S, Barrio L, Jongsma H, Gros D, van Rijen H : Replacement of connexin40 in the mouse: impact on cardiac electrical conduction. Circ Res 2004 94 : 100 109.
80. Miquerol L, Meysen S, Mangoni M, Bois P, van Rijen HVM, Abran P, Jongsma H, Nargeot J, Gros D : Architectural and functional asymmetry of the His-Purkinje system of the murine heart. Cardiovasc Res 2004 63 : 77 86.
81. Temple J, Frias P, Rottman J, Yang T, Wu Y, Verheijck EE, Zhang W, Siprachanh C, Kanki H, Atkinson JB, King P, Anderson ME, Kupershmidt S, Roden DM : Atrial fibrillation in KCNE1-null mice. Circ Res 2005 97 : 62 69.