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Bigenic Mice (bigenic + mouse)
Selected AbstractsCognitive and non-cognitive behaviors in an APPswe/PS1 bigenic model of Alzheimer's diseaseGENES, BRAIN AND BEHAVIOR, Issue 2 2009M. Filali Neuropsychiatric signs are critical in primary caregiving of Alzheimer patients and yet have been relatively ignored in murine models. In the present study, APPswe/PS1 bigenic mice had higher levels of irritability than non-transgenic controls as measured in the touch escape test. Moreover, APPswe/PS1 mice showed poorer nest building than controls and a higher duration of immobility in the forced swimming assay. These results are concordant with the hypothesis of increased apathy and depression-like behavior in an Alzheimer's disease model. In addition, APPswe/PS1 bigenic mice were deficient in retention of passive avoidance learning and left,right discrimination learning, concordant with previous findings in other Alzheimer-like models. [source] Hepsin cooperates with MYC in the progression of adenocarcinoma in a prostate cancer mouse modelTHE PROSTATE, Issue 6 2010Srinivas Nandana Abstract BACKGROUND Hepsin is a cell surface protease that is over-expressed in more than 90% of human prostate cancer cases. The previously developed Probasin-hepsin/Large Probasin-T antigen (PB-hepsin/LPB-Tag) bigenic mouse model of prostate cancer demonstrates that hepsin promotes primary tumors that are a mixture of adenocarcinoma and neuroendocrine (NE) lesions, and metastases that are NE in nature. However, since the majority of human prostate tumors are adenocarcinomas, the contribution of hepsin in the progression of adenocarcinoma requires further investigation. METHODS We crossed the PB-hepsin mice with PB-Hi-myc transgenic mouse model of prostate adenocarcinoma and characterized the tumor progression in the resulting PB-hepsin/PB-Hi-myc bigenic mice. RESULTS We report that PB-hepsin/PB-Hi-myc bigenic mice develop invasive adenocarcinoma at 4.5 months. Further, histological analysis of the 12- to 17-month-old mice revealed that the PB-hepsin/PB-Hi-myc model develops a higher grade adenocarcinoma compared with age-matched tumors expressing only PB-Hi-myc. Consistent with targeting hepsin to the prostate, the PB-hepsin/PB-Hi-myc tumors showed higher hepsin expression as compared to the age-matched myc tumors. Furthermore, endogenous expression of hepsin increased in the PB-Hi-myc mice as the tumors progressed. CONCLUSIONS Although we did not detect any metastases from the prostates in either the PB-hepsin/PB-Hi-myc or the PB-Hi-myc mice, our data suggests that hepsin and myc cooperate during the progression to high-grade prostatic adenocarcinoma. Prostate 70: 591,600, 2010. © 2009 Wiley-Liss, Inc. [source] Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid-, oligomersANNALS OF NEUROLOGY, Issue 2 2010Sam Gandy MD Objective Recent evidence suggests that high molecular weight soluble oligomeric A, (oA,) assemblies (also known as A,-derived diffusible ligands, or ADDLs) may represent a primary neurotoxic basis for cognitive failure in Alzheimer disease (AD). To date, most in vivo studies of oA,/ADDLs have involved injection of assemblies purified from the cerebrospinal fluid of human subjects with AD or from the conditioned media of A,-secreting cells into experimental animals. We sought to study the bioactivities of endogenously formed oA,/ADDLs generated in situ from the physiological processing of human amyloid precursor protein (APP) and presenitin1 (PS1) transgenes. Methods We produced and histologically characterized single transgenic mice overexpressing APPE693Q or APPE693Q X PS1,E9 bigenic mice. APPE693Q mice were studied in the Morris water maze (MWM) task at 6 and 12 months of age. Following the second MWM evaluation, mice were sacrificed, and brains were assayed for A,total, A,40, A,42, and oA,/ADDLs by enzyme-linked immunosorbent assay (ELISA) and were also histologically examined. Based on results from the oA,/ADDL ELISA, we assigned individual APPE693Q mice to either an undetectable oA,/ADDLs group or a readily detectable oA,/ADDLs group. A days to criterion (DTC) analysis was used to determine delays in acquisition of the MWM task. Results Both single transgenic and bigenic mice developed intraneuronal accumulation of APP/A,, although only APPE693Q X PS1,9 bigenic mice developed amyloid plaques. The APPE693Q mice did not develop amyloid plaques at any age studied, up to 30 months. APPE693Q mice were tested for spatial learning and memory, and only 12-month-old APPE693Q mice with readily detectable oA,/ADDLs displayed a significant delay in acquisition of the MWM task when compared to nontransgenic littermates. Interpretation These data suggest that cerebral oA,/ADDL assemblies generated in brain in situ from human APP transgenes may be associated with cognitive impairment. We propose that a DTC analysis may be a sensitive method for assessing the cognitive impact in mice of endogenously generated oligomeric human A, assemblies. ANN NEUROL 2010 [source] | ||||||||||