Methodology Aspects of Colony Maintain for a Murine Model of Amyotrophic Lateral Sclerosis (ALS) TDP-43 Proteinopathy

Autor: Agueda Ferrer-Donato, César Álvaro-Alonso, Elizabeth Fernández-Torres, Mónica Carballo-Villa, Carmen M. Fernandez-Martos
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Animals, Vol 10, Iss 2329, p 2329 (2020)
Animals : an Open Access Journal from MDPI
Animals
Volume 10
Issue 12
ISSN: 2076-2615
Popis: Simple Summary Rodent models of central nervous system (CNS) disorders are widely used to explore pathology and molecular mechanisms of disease. These models are a valuable tool for understanding the genetic basis of amyotrophic lateral sclerosis (ALS) research, a CNS disease that affects motor neurons in the brain and spinal cord, causing loss of voluntary muscle control. There are two different types of ALS: Sporadic (sALS), accounts for 90 to 95 percent of all cases, which means the disease seems to occur at random with no clearly associated risk factors and no family history of the disease, and familial (fALS), which is inherited and accounts for 5 to 10 percent of all cases. One example of a gene mutation in fALS is the A315T mutation to the gene encoding TDP-43. The congenic Prp-TDP43A315T Tg model of ALS disease expresses full-length human TARDBP containing this mutation. The effects of the highly aggressive phenotype of this Tg model of human ALS, and its premature sudden death prior to full development of neurodegenerative symptoms, makes it essential to determine their reproductive pattern in order to guarantee proper colony maintenance, which is the main goal of this study. 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.
Databáze: OpenAIRE
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