Protocols


Screen (pdf version)
ScreenBlood Pressure
Posted On03/17/2017 3:22 PM
AuthorSamantha Kuwada Teixeira
Background

High blood pressure affects millions of people worldwide and is a major risk factor for cardiovascular disease (1;2). In nearly 95 per cent of hypertensive patients it is a complex disease in which the heritability of systolic and diastolic blood pressure components range from 25 to 68 per cent (3-5). Genomic strategies such as GWAS unveiled 100s of gene variants, even though they individually or in combination explain no more than 1-2 percent of the blood pressure variance (6).  In addition, we and others have spent enormous amount of time and resources performing BP QTL fine mapping in genetic crosses of hypertensive rat models with limited success (7-9). In this context, systematic ENU strategy developed in the Beutler’s lab offers a unique opportunity to map BP gene variants in mice and their biochemical role, which may shed light on the candidate gene/pathways affecting hypertensive patients. The objective is to identify BP genes using ENU technology and experimental design from Beutler’s lab.

Method

We are using a noninvasive screen to measure blood pressure in conscious mice using plethysmography. Each animal is placed in a sensing holder for 20 minutes for blood pressure measurement (18 mice at a time). Each measurement consists in averaging the values of 10 assessments performed automatically with a 15 second-interval between them. We repeat this procedure in three subsequent days for each animal.  We use the first day to train the animals with the plethysmograph apparatus and the effective BP measurement is performed on the second and third day. We register together the animals from each pedigree (50-70 animals per day). Body weight was measured on the last day.

Critical Parameters and Troubleshooting

Body weight, age and gender are collected together with blood pressure to assess if these variables influencing the phenotype. Moreover, data along age are being collected from C57 mice.

References
  6. International Consortium for Blood Pressure Genome-Wide Association Studies, Ehret, G. B., Munroe, P. B., Rice, K. M., Bochud, M., Johnson, A. D., Chasman, D. I., Smith, A. V., Tobin, M. D., Verwoert, G. C., Hwang, S. J., Pihur, V., Vollenweider, P., O'Reilly, P. F., Amin, N., Bragg-Gresham, J. L., Teumer, A., Glazer, N. L., Launer, L., Zhao, J. H., Aulchenko, Y., Heath, S., Sober, S., Parsa, A., Luan, J., Arora, P., Dehghan, A., Zhang, F., Lucas, G., Hicks, A. A., Jackson, A. U., Peden, J. F., Tanaka, T., Wild, S. H., Rudan, I., Igl, W., Milaneschi, Y., Parker, A. N., Fava, C., Chambers, J. C., Fox, E. R., Kumari, M., Go, M. J., van der Harst, P., Kao, W. H., Sjogren, M., Vinay, D. G., Alexander, M., Tabara, Y., Shaw-Hawkins, S., Whincup, P. H., Liu, Y., Shi, G., Kuusisto, J., Tayo, B., Seielstad, M., Sim, X., Nguyen, K. D., Lehtimaki, T., Matullo, G., Wu, Y., Gaunt, T. R., Onland-Moret, N. C., Cooper, M. N., Platou, C. G., Org, E., Hardy, R., Dahgam, S., Palmen, J., Vitart, V., Braund, P. S., Kuznetsova, T., Uiterwaal, C. S., Adeyemo, A., Palmas, W., Campbell, H., Ludwig, B., Tomaszewski, M., Tzoulaki, I., Palmer, N. D., CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Aspelund, T., Garcia, M., Chang, Y. P., O'Connell, J. R., Steinle, N. I., Grobbee, D. E., Arking, D. E., Kardia, S. L., Morrison, A. C., Hernandez, D., Najjar, S., McArdle, W. L., Hadley, D., Brown, M. J., Connell, J. M., Hingorani, A. D., Day, I. N., Lawlor, D. A., Beilby, J. P., Lawrence, R. W., Clarke, R., Hopewell, J. C., Ongen, H., Dreisbach, A. W., Li, Y., Young, J. H., Bis, J. C., Kahonen, M., Viikari, J., Adair, L. S., Lee, N. R., Chen, M. H., Olden, M., Pattaro, C., Bolton, J. A., Kottgen, A., Bergmann, S., Mooser, V., Chaturvedi, N., Frayling, T. M., Islam, M., Jafar, T. H., Erdmann, J., Kulkarni, S. R., Bornstein, S. R., Grassler, J., Groop, L., Voight, B. F., Kettunen, J., Howard, P., Taylor, A., Guarrera, S., Ricceri, F., Emilsson, V., Plump, A., Barroso, I., Khaw, K. T., Weder, A. B., Hunt, S. C., Sun, Y. V., Bergman, R. N., Collins, F. S., Bonnycastle, L. L., Scott, L. J., Stringham, H. M., Peltonen, L., Perola, M., Vartiainen, E., Brand, S. M., Staessen, J. A., Wang, T. J., Burton, P. R., Soler Artigas, M., Dong, Y., Snieder, H., Wang, X., Zhu, H., Lohman, K. K., Rudock, M. E., Heckbert, S. R., Smith, N. L., Wiggins, K. L., Doumatey, A., Shriner, D., Veldre, G., Viigimaa, M., Kinra, S., Prabhakaran, D., Tripathy, V., Langefeld, C. D., Rosengren, A., Thelle, D. S., Corsi, A. M., Singleton, A., Forrester, T., Hilton, G., McKenzie, C. A., Salako, T., Iwai, N., Kita, Y., Ogihara, T., Ohkubo, T., Okamura, T., Ueshima, H., Umemura, S., Eyheramendy, S., Meitinger, T., Wichmann, H. E., Cho, Y. S., Kim, H. L., Lee, J. Y., Scott, J., Sehmi, J. S., Zhang, W., Hedblad, B., Nilsson, P., Smith, G. D., Wong, A., Narisu, N., Stancakova, A., Raffel, L. J., Yao, J., Kathiresan, S., O'Donnell, C. J., Schwartz, S. M., Ikram, M. A., Longstreth, W. T.,Jr, Mosley, T. H., Seshadri, S., Shrine, N. R., Wain, L. V., Morken, M. A., Swift, A. J., Laitinen, J., Prokopenko, I., Zitting, P., Cooper, J. A., Humphries, S. E., Danesh, J., Rasheed, A., Goel, A., Hamsten, A., Watkins, H., Bakker, S. J., van Gilst, W. H., Janipalli, C. S., Mani, K. R., Yajnik, C. S., Hofman, A., Mattace-Raso, F. U., Oostra, B. A., Demirkan, A., Isaacs, A., Rivadeneira, F., Lakatta, E. G., Orru, M., Scuteri, A., Ala-Korpela, M., Kangas, A. J., Lyytikainen, L. P., Soininen, P., Tukiainen, T., Wurtz, P., Ong, R. T., Dorr, M., Kroemer, H. K., Volker, U., Volzke, H., Galan, P., Hercberg, S., Lathrop, M., Zelenika, D., Deloukas, P., Mangino, M., Spector, T. D., Zhai, G., Meschia, J. F., Nalls, M. A., Sharma, P., Terzic, J., Kumar, M. V., Denniff, M., Zukowska-Szczechowska, E., Wagenknecht, L. E., Fowkes, F. G., Charchar, F. J., Schwarz, P. E., Hayward, C., Guo, X., Rotimi, C., Bots, M. L., Brand, E., Samani, N. J., Polasek, O., Talmud, P. J., Nyberg, F., Kuh, D., Laan, M., Hveem, K., Palmer, L. J., van der Schouw, Y. T., Casas, J. P., Mohlke, K. L., Vineis, P., Raitakari, O., Ganesh, S. K., Wong, T. Y., Tai, E. S., Cooper, R. S., Laakso, M., Rao, D. C., Harris, T. B., Morris, R. W., Dominiczak, A. F., Kivimaki, M., Marmot, M. G., Miki, T., Saleheen, D., Chandak, G. R., Coresh, J., Navis, G., Salomaa, V., Han, B. G., Zhu, X., Kooner, J. S., Melander, O., Ridker, P. M., Bandinelli, S., Gyllensten, U. B., Wright, A. F., Wilson, J. F., Ferrucci, L., Farrall, M., Tuomilehto, J., Pramstaller, P. P., Elosua, R., Soranzo, N., Sijbrands, E. J., Altshuler, D., Loos, R. J., Shuldiner, A. R., Gieger, C., Meneton, P., Uitterlinden, A. G., Wareham, N. J., Gudnason, V., Rotter, J. I., Rettig, R., Uda, M., Strachan, D. P., Witteman, J. C., Hartikainen, A. L., Beckmann, J. S., Boerwinkle, E., Vasan, R. S., Boehnke, M., Larson, M. G., Jarvelin, M. R., Psaty, B. M., Abecasis, G. R., Chakravarti, A., Elliott, P., van Duijn, C. M., Newton-Cheh, C., Levy, D., Caulfield, M. J., and Johnson, T. (2011) Genetic Variants in Novel Pathways Influence Blood Pressure and Cardiovascular Disease Risk. Nature. 478, 103-109.