title: Time to Integrate to Nest Test Evaluation in a Mouse DSS-Colitis Model.
abstract: Severity assessment in laboratory animals is an important issue regarding the implementation of the 3R concept into biomedical research and pivotal in current EU regulations. In mouse models of inflammatory bowel disease severity assessment is usually undertaken by clinical scoring, especially by monitoring reduction of body weight. This requires daily observance and handling of each mouse, which is time consuming, stressful for the animal and necessitates an experienced observer. The time to integrate to nest test (TINT) is an easily applicable test detecting disturbed welfare by measuring the time interval mice need to integrate nesting material to an existing nest. Here, TINT was utilized to assess severity in a mouse DSS-colitis model. TINT results depended on the group size of mice maintained per cage with most consistent time intervals measured when co-housing 4 to 5 mice. Colitis was induced with 1% or 1.5% DSS in group-housed WT and Cd14-deficient mice. Higher clinical scores and loss of body weight were detected in 1.5% compared to 1% DSS treated mice. TINT time intervals showed no dose dependent differences. However, increased clinical scores, body weight reductions, and increased TINT time intervals were detected in Cd14-/- compared to WT mice revealing mouse strain related differences. Therefore, TINT is an easily applicable method for severity assessment in a mouse colitis model detecting CD14 related differences, but not dose dependent differences. As TINT revealed most consistent results in group-housed mice, we recommend utilization as an additional method substituting clinical monitoring of the individual mouse.
authors.affiliation: Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Häger
authors.affiliation: Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Keubler
authors.affiliation: Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Biernot
authors.affiliation: Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Dietrich
authors.affiliation: Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Buchheister
authors.affiliation: Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Buettner
authors.affiliation: Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Bleich
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009425:Nesting Behavior / Q000187:drug effects*
chemical_list: D018950:Lipopolysaccharide Receptors; D016264:Dextran Sulfate