Phenotypic screening of hepatocyte nuclear factor (HNF) 4-gamma receptor knockout mice. Export

@article{citeulike:2192647, abstract = {Using the mouse as a model organism in pharmaceutical research presents unique advantages as its physiology in many ways resembles the human physiology, it also has a relatively short generation time, low breeding and maintenance costs, and is available in a wide variety of inbred strains. The ability to genetically modify mouse embryonic stem cells to generate mouse models that better mimic human disease is another advantage. In the present study, a comprehensive phenotypic screening protocol is applied to elucidate the phenotype of a novel mouse knockout model of hepatocyte nuclear factor (HNF) 4-gamma. HNF4-gamma is expressed in the kidneys, gut, pancreas, and testis. The first level of the screen is aimed at general health, morphologic appearance, normal cage behaviour, and gross neurological functions. The second level of the screen looks at metabolic characteristics and lung function. The third level of the screen investigates behaviour more in-depth and the fourth level consists of a thorough pathological characterisation, blood chemistry, haematology, and bone marrow analysis. When compared with littermate wild-type mice (HNF4-gamma(+/+)), the HNF4-gamma knockout (HNF4-gamma(-/-)) mice had lowered energy expenditure and locomotor activity during night time that resulted in a higher body weight despite having reduced intake of food and water. HNF4-gamma(-/-) mice were less inclined to build nest and were found to spend more time in a passive state during the forced swim test.}, address = {AstraZeneca Transgenic and Comparative Genomics, AstraZeneca R\&D, M\"{o}lndal, Sweden.}, author = {Gerdin, A. K. and Surve, V. V. and J\"{o}nsson, M. and Bjursell, M. and Bj\"{o}rkman, M. and Edenro, A. and Schuelke, M. and Saad, A. and Bjurstr\"{o}m, S. and Lundgren, E. J. and Snaith, M. and Fransson-Steen, R. and T\"{o}rnell, J. and Berg, A. L. and Bohlooly-Y, M.}, citeulike-article-id = {2192647}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bbrc.2006.08.103}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16945327}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16945327}, day = {20}, doi = {10.1016/j.bbrc.2006.08.103}, issn = {0006-291X}, journal = {Biochem Biophys Res Commun}, keywords = {expression, hnf4gamma, knockout}, month = {October}, number = {2}, pages = {825--832}, posted-at = {2008-01-03 23:33:55}, priority = {2}, title = {Phenotypic screening of hepatocyte nuclear factor (HNF) 4-gamma receptor knockout mice.}, url = {http://dx.doi.org/10.1016/j.bbrc.2006.08.103}, volume = {349}, year = {2006} }

TY - JOUR ID - citeulike:2192647 L3 - citeulike-article-id:2192647 N2 - Using the mouse as a model organism in pharmaceutical research presents unique advantages as its physiology in many ways resembles the human physiology, it also has a relatively short generation time, low breeding and maintenance costs, and is available in a wide variety of inbred strains. The ability to genetically modify mouse embryonic stem cells to generate mouse models that better mimic human disease is another advantage. In the present study, a comprehensive phenotypic screening protocol is applied to elucidate the phenotype of a novel mouse knockout model of hepatocyte nuclear factor (HNF) 4-gamma. HNF4-gamma is expressed in the kidneys, gut, pancreas, and testis. The first level of the screen is aimed at general health, morphologic appearance, normal cage behaviour, and gross neurological functions. The second level of the screen looks at metabolic characteristics and lung function. The third level of the screen investigates behaviour more in-depth and the fourth level consists of a thorough pathological characterisation, blood chemistry, haematology, and bone marrow analysis. When compared with littermate wild-type mice (HNF4-gamma(+/+)), the HNF4-gamma knockout (HNF4-gamma(-/-)) mice had lowered energy expenditure and locomotor activity during night time that resulted in a higher body weight despite having reduced intake of food and water. HNF4-gamma(-/-) mice were less inclined to build nest and were found to spend more time in a passive state during the forced swim test. IS - 2 JF - Biochem Biophys Res Commun SN - 0006-291X AD - AstraZeneca Transgenic and Comparative Genomics, AstraZeneca R&D, Mölndal, Sweden. EP - 832 TI - Phenotypic screening of hepatocyte nuclear factor (HNF) 4-gamma receptor knockout mice. VL - 349 SP - 825 KW - expression KW - hnf4gamma KW - knockout AU - Gerdin, AK AU - Surve, VV AU - Jönsson, M AU - Bjursell, M AU - Björkman, M AU - Edenro, A AU - Schuelke, M AU - Saad, A AU - Bjurström, S AU - Lundgren, EJ AU - Snaith, M AU - Fransson-Steen, R AU - Törnell, J AU - Berg, AL AU - Bohlooly-Y, M PY - 2006/10/20/ UR - http://dx.doi.org/10.1016/j.bbrc.2006.08.103 ER -