title: Influence of genetic background and gender on bladder function in the mouse.
abstract: Genetically targeted animals are used throughout research to investigate the role genes play in biological function, including the lower urinary tract. Generation of transgenic mice involves backcrossing for successive generations. Parental strain background genes can interact with the mutated gene potentially affecting interpretation of the mutant phenotype. Differences in physiological phenotypes may also be influenced by gender. The present study evaluated bladder function in five strains of male and female mice, 129S6/SvEvTac, A/J, B6129F1/Tac, BALB/cAnNCrL and C57BL/6NTacFBr. Urodynamic parameters were analyzed during infusion of saline (threshold and void volume, non-voiding contractions, pressure threshold and bladder contraction amplitude) in conscious mice and using voluntary urination in freely moving mice placed on filter paper (number of small and large diameter urine spots), which represent commonly used techniques in preclinical characterization of bladder function. Female BALB/c mice exhibited a significantly larger number of non-voiding contractions and urine dripping (increased number of small urine spots) compared to other female mice. Male BALB/c mice did not share this phenotype. Significant differences in threshold and void volumes were also noted amongst strains and genders. The numbers of large diameter urine spots differed amongst female, and not male, mouse strains. Gender differences were observed between sexes of the same strain in both large and small urine spots. These data demonstrate that genetic background and gender can influence bladder function in the mouse. These differences have a significant impact on the choice of strain and gender when investigating the effects of genetic manipulation on the micturition reflex.
authors.affiliation: Urogenital Biology, Cardiovascular & Urogenital Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, Philadelphia, PA 19406, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Cornelissen
authors.forename: Blake
authors.initials: B
authors.lastname: Misajet
authors.forename: David P
authors.initials: DP
authors.lastname: Brooks
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hicks
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000235:genetics; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D010641:Phenotype; D011312:Pressure; D012018:Reflex / Q000235:genetics; D012727:Sex Characteristics; D012737:Sex Factors; D013045:Species Specificity; D001743:Urinary Bladder / Q000294:innervation / Q000502:physiology*; D014554:Urination / Q000235:genetics* / Q000502:physiology*; D014555:Urination Disorders / Q000235:genetics / Q000503:physiopathology