WS07.3 Phenotypic and genotypic characterisation of a novel mouse model of F508del-CFTR in genetically diverse collaborative cross

2021 ◽  
Vol 20 ◽  
pp. S13
Author(s):  
B. Sipione ◽  
N.I. Lorè ◽  
G. Rossi ◽  
F. Sanvito ◽  
M. D'Aurora ◽  
...  
Gut ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 1942-1952 ◽  
Author(s):  
Pin Wang ◽  
Yunshan Wang ◽  
Sasha A Langley ◽  
Yan-Xia Zhou ◽  
Kuang-Yu Jen ◽  
...  

ObjectiveThe Collaborative Cross (CC) is a mouse population model with diverse and reproducible genetic backgrounds used to identify novel disease models and genes that contribute to human disease. Since spontaneous tumour susceptibility in CC mice remains unexplored, we assessed tumour incidence and spectrum.DesignWe monitored 293 mice from 18 CC strains for tumour development. Genetic association analysis and RNA sequencing were used to identify susceptibility loci and candidate genes. We analysed genomes of patients with gastric cancer to evaluate the relevance of genes identified in the CC mouse model and measured the expression levels of ISG15 by immunohistochemical staining using a gastric adenocarcinoma tissue microarray. Association of gene expression with overall survival (OS) was assessed by Kaplan-Meier analysis.ResultsCC mice displayed a wide range in the incidence and types of spontaneous tumours. More than 40% of CC036 mice developed gastric tumours within 1 year. Genetic association analysis identified Nfκb1 as a candidate susceptibility gene, while RNA sequencing analysis of non-tumour gastric tissues from CC036 mice showed significantly higher expression of inflammatory response genes. In human gastric cancers, the majority of human orthologues of the 166 mouse genes were preferentially altered by amplification or deletion and were significantly associated with OS. Higher expression of the CC036 inflammatory response gene signature is associated with poor OS. Finally, ISG15 protein is elevated in gastric adenocarcinomas and correlated with shortened patient OS.ConclusionsCC strains exhibit tremendous variation in tumour susceptibility, and we present CC036 as a spontaneous laboratory mouse model for studying human gastric tumourigenesis.


2020 ◽  
Vol 34 (6) ◽  
pp. 7773-7785
Author(s):  
Aline Conti ◽  
Volodymyr Tryndyak ◽  
Rose A. Willett ◽  
Barbara Borowa‐Mazgaj ◽  
Anna Watson ◽  
...  

2018 ◽  
Vol 29 (7-8) ◽  
pp. 471-487 ◽  
Author(s):  
Hanifa Abu Toamih Atamni ◽  
Aysar Nashef ◽  
Fuad A. Iraqi

2014 ◽  
Vol 25 (3-4) ◽  
pp. 95-108 ◽  
Author(s):  
Allison R. Rogala ◽  
Andrew P. Morgan ◽  
Alexis M. Christensen ◽  
Terry J. Gooch ◽  
Timothy A. Bell ◽  
...  

Author(s):  
H. D. Geissinge ◽  
L.D. Rhodes

A recently discovered mouse model (‘mdx’) for muscular dystrophy in man may be of considerable interest, since the disease in ‘mdx’ mice is inherited by the same mode of inheritance (X-linked) as the human Duchenne (DMD) muscular dystrophy. Unlike DMD, which results in a situation in which the continual muscle destruction cannot keep up with abortive regenerative attempts of the musculature, and the sufferers of the disease die early, the disease in ‘mdx’ mice appears to be transient, and the mice do not die as a result of it. In fact, it has been reported that the severely damaged Tibialis anterior (TA) muscles of ‘mdx’ mice seem to display exceptionally good regenerative powers at 4-6 weeks, so much so, that these muscles are able to regenerate spontaneously up to their previous levels of physiological activity.


1998 ◽  
Vol 13 (11-s4) ◽  
pp. S178-S184 ◽  
Author(s):  
PETER KONTUREK ◽  
TOMASZ BRZOZOWSKI ◽  
STANISLAW KONTUREK ◽  
ELZBIETA KARCZEWSKA ◽  
ROBERT PAJDO ◽  
...  

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