title: Phenotypic screening of hepatocyte nuclear factor (HNF) 4-gamma receptor knockout mice.
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.
authors.affiliation: AstraZeneca Transgenic and Comparative Genomics, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Anna Karin
authors.initials: AK
authors.lastname: Gerdin
authors.forename: Vikas V
authors.initials: VV
authors.lastname: Surve
authors.forename: Marie
authors.initials: M
authors.lastname: Jönsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Bjursell
authors.forename: Maria
authors.initials: M
authors.lastname: Björkman
authors.forename: Anne
authors.initials: A
authors.lastname: Edenro
authors.forename: Meint
authors.initials: M
authors.lastname: Schuelke
authors.forename: Alaa
authors.initials: A
authors.lastname: Saad
authors.forename: Sivert
authors.initials: S
authors.lastname: Bjurström
authors.forename: Elisabeth Jensen
authors.initials: EJ
authors.lastname: Lundgren
authors.forename: Michael
authors.initials: M
authors.lastname: Snaith
authors.forename: Ronny
authors.initials: R
authors.lastname: Fransson-Steen
authors.forename: Jan
authors.initials: J
authors.lastname: Törnell
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Berg
authors.forename: Mohammad
authors.initials: M
authors.lastname: Bohlooly-Y
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D001853:Bone Marrow / Q000378:metabolism; D002151:Calorimetry; D005260:Female; D051557:Hepatocyte Nuclear Factor 4 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D010101:Oxygen Consumption; D010641:Phenotype
chemical_list: D051557:Hepatocyte Nuclear Factor 4; C496598:Hnf4g protein, mouse