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Methodology aspects of colony maintain for a murine model of amyotrophic lateral sclerosis (ALS) TDP-43 proteinopathy

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Alvaro-Alonso, C, Ferrer-Donato, A, Fernandez-Torres, E, Carballo-Villa, M and Fernandez-Martos, CM ORCID: 0000-0002-6387-4456 2020 , 'Methodology aspects of colony maintain for a murine model of amyotrophic lateral sclerosis (ALS) TDP-43 proteinopathy' , Animals, vol. 10, no. 12 , pp. 1-9 , doi: 10.3390/ani10122329.

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Abstract

The use of genetically engineered mouse (GEMs) models provides an unprecedented opportunity to study the genetic basis of diseases and gene function, therefore it is paramount to determine reproductive parameters that guarantee proper colony maintenance. We studied the reproductive parameters of mice hemizygous for TDP-43A315T transgene, which are viable, fertile, and express a mutant human TAR DNA binding protein (hTDP-43) cDNA harboring an amino acid substitution associated with familial amyotrophic lateral sclerosis (fALS). TDP43A315T mice were backcrossed to a C57Bl6/J pure background for four consecutive generations. The Tg offspring genotype were then confirmed by PCR assays. Our statistical analysis indicated there were no differences in the sex and number of pups per offspring when hemizygous female and male TDP43A315T mice were backcrossed to C57Bl6/J mice. Interestingly, our results showed significant differences in the number of offspring expressing the transgene when hemizygous TDP43A315T male mice were used as breeders. Therefore, our findings suggest that male TDP43A315T mice transfer the transgene with a greater genetic strengths. Such is an important breeding consideration to ensure the principle of reduction in animal experimentation considering most basic research with models focuses on males and excludes female mice.

Item Type: Article
Authors/Creators:Alvaro-Alonso, C and Ferrer-Donato, A and Fernandez-Torres, E and Carballo-Villa, M and Fernandez-Martos, CM
Keywords: genetically engineered mouse (GEMs), TAR DNA binding protein (TDP-43), amyotrophic lateral sclerosis (ALS)
Journal or Publication Title: Animals
Publisher: MDPIAG
ISSN: 2076-2615
DOI / ID Number: 10.3390/ani10122329
Copyright Information:

Copyright 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license http://creativecommons.org/licenses/by/4.0/).

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