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These complementary results, which were obtained independently using distinct experimental methods and different mouse backgrounds, provide compelling evidence for predominant neuron-autonomous mechanisms of toxicity in NPC disease.
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Derivation of MINOs from a variety of genetically engineered mice backgrounds may provide additional critical reagents for the preclinical study of DCIS.
Animal models provide support for this view, since they show homogeneous disease phenotypes, where variation can be introduced through environmental actions such as exercise and environmental enrichment and through mouse strain genetic background, providing a model for the amyloid hypothesis.
ApoE-/ mice with the C57BL/6 genetic background, provided by Joslin Diabetes Center (Boston, MA, USA), were bred in a pathogen-free environment with a 12 h light/dark cycle and free access to food and water.
BACE1 −/− mice were obtained from GlaxoSmithKline and were continued on the C57Bl6/J background, providing BACE1 −/− and BACE1 +/− mice and WT (wild-type) littermates.
Transgenic K-ras LA1/+ mice 1, 2, 11 were on an 129/Sv background (provided by G. Lozano, MD Anderson Cancer Center) 1, 2, 11.
The genetic background provides a susceptibility to the development of hepatic steatosis such as in the SV129S6 mouse [ 72].
Mice genetically engineered to express human PrP on a nullizygous mouse PrP background have provided new animal models in which to propagate and study the properties of BSE/vCJD agent.
After intercrossing this mouse with proximal Lck promoter (Lck)- Cre transgenic mice (C57BL/6J background, kindly provided by Dr. Junji Takeda, Osaka University) [ 18], Cxcr4 flox/+/ Lck-Cre mice were backcrossed to the DBA/1J mice (Charles River Laboratories) for eight generations.
The organs of Corti from wild-type P4 mice (background 129S5) were kindly provided by prof.
Because global miRNA biogenesis has been blocked in DGCR8- or Dicer-knockout mice, these strains provide a clean background to identify the core set of miRNAs that are sufficient to support brown fat development.
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