Journal ArticleDOI
Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment
Derek C. Rogers,Elizabeth M. C. Fisher,Steve D.M. Brown,Josephine Peters,A. J. Hunter,Joanne E. Martin +5 more
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TLDR
The SHIRPA procedure is developed, which utilizes standardized protocols for behavioral and functional assessment that provide a sensitive measure for quantifying phenotype expression in the mouse, and can be refined to test the function of specific neural pathways, which will contribute to a greater understanding of neurological disorders.Abstract:
For an understanding of the aberrant biology seen in mouse mutations and identification of more subtle phenotype variation, there is a need for a full clinical and pathological characterization of the animals. Although there has been some use of sophisticated techniques, the majority of behavioral and functional analyses in mice have been qualitative rather than quantitative in nature. There is, however, no comprehensive routine screening and testing protocol designed to identify and characterize phenotype variation or disorders associated with the mouse genome. We have developed the SHIRPA procedure to characterize the phenotype of mice in three stages. The primary screen utilizes standard methods to provide a behavioral and functional profile by observational assessment. The secondary screen involves a comprehensive behavioral assessment battery and pathological analysis. These protocols provide the framework for a general phenotype assessment that is suitable for a wide range of applications, including the characterization of spontaneous and induced mutants, the analysis of transgenic and gene-targeted phenotypes, and the definition of variation between strains. The tertiary screening stage described is tailored to the assessment of existing or potential models of neurological disease, as well as the assessment of phenotypic variability that may be the result of unknown genetic influences. SHIRPA utilizes standardized protocols for behavioral and functional assessment that provide a sensitive measure for quantifying phenotype expression in the mouse. These paradigms can be refined to test the function of specific neural pathways, which will, in turn, contribute to a greater understanding of neurological disorders.read more
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Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.
Brinda Ravikumar,Coralie Vacher,Zdenek Berger,Janet E. Davies,Shouqing Luo,Lourdes Garcia Oroz,Francesco Scaravilli,Douglas F. Easton,Rainer Duden,Cahir J. O'Kane,David C. Rubinsztein +10 more
TL;DR: This work shows that mammalian target of rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models, transgenic mice and human brains, and provides proof-of-principle for the potential of inducing autophagy to treat Huntington disease.
Journal ArticleDOI
Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia
John B. Davis,Julie E. Gray,Martin J. Gunthorpe,Jonathan P. Hatcher,Phil T. Davey,Philip Overend,Mark H Harries,Judi Latcham,Colin M. Clapham,Kirsty Atkinson,Stephen A. Hughes,Kim Rance,Evelyn Grau,Alex J. Harper,Perdita L. Pugh,Derek C. Rogers,Sharon Bingham,Andrew D. Randall,Steven A. Sheardown +18 more
TL;DR: It is concluded that VR1 is required for inflammatory sensitization to noxious thermal stimuli but also that alternative mechanisms are sufficient for normal sensation of noxious heat.
Journal ArticleDOI
A mouse Mecp2-null mutation causes neurological symptoms that mimic rett syndrome
TL;DR: The overlapping delay before symptom onset in humans and mice raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2, and generates mice lacking Mecp2 using Cre-loxP technology.
Journal ArticleDOI
BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics.
Steven L. Roberds,John P. Anderson,Guriqbal Basi,Michael Jerome Bienkowski,Daniel G. Branstetter,Karen S. Chen,Stephen B. Freedman,Normand Frigon,Dora Kate Games,Kang Hu,Kelly Johnson-Wood,Karl Kappenman,Thomas T. Kawabe,Ismail Kola,Ralf Kuehn,Mike Lee,Weiqun Liu,Ruth Motter,Nanette F. Nichols,Michael Power,David W. Robertson,Dale Schenk,Michael Schoor,George Shopp,Mary E. Shuck,Sukanto Sinha,Kjell A. Svensson,Gwen Tatsuno,Hartmut Tintrup,John A. Wijsman,Sarah Wright,Lisa McConlogue +31 more
TL;DR: The findings that BACE is the primary beta- secretase activity in brain and that loss of beta-secretase activity produces no profound phenotypic defects with a concomitant reduction in beta-amyloid peptide clearly indicate that Bace is an excellent therapeutic target for treatment of AD.
Journal ArticleDOI
H2S Induces a Suspended AnimationLike State in Mice
TL;DR: It is reported that hydrogen sulfide can induce a suspended animation-like state in a nonhibernating species, the house mouse (Mus musculus), and this state is readily reversible and does not appear to harm the animal.
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