We will cover three basic steps in model design: (1) identifying the strain background to modify using phenotypic profiles, (2) identifying the allele to introduce using genomic and transcriptomic information, and (3) choosing and implementing the methodology for introducing the allele.

Neonatal hydrocephalus has been analyzed using two different models of mutated rats, one with an invalidation of the L1cam gene (Emmert et al., 2019b) and the other with a KI of a specific mutation in the Ccdc39 gene (Emmert et al., 2019a). These models allow for neurosurgery procedures that are difficult to perform in mice, with resulting ...

Unfortunately, our ability to manipulate the rat genome has lagged behind that of the mouse, with its seemingly endless possibilities in reverse genetics and standardized mutant phenotyping protocols [8,9] (Figure 1). However, the rat genetic toolbox is developing rapidly as a result of several significant technological advances, including the ...

Nov 20, 2017 · Random mutagenesis can induce mutations throughout the rat genome by introducing a transposon such as Sleeping Beauty or a chemical mutagen such as N-ethyl-N-nitrosourea (ENU) [20, 21]. However,...

This chapter describes the use of zinc-finger nucleases (ZFNs) for the targeted disruption of endogenous rat genes directly in the embryo. ZFNs can specifically disrupt target genes in cultured rat cells and in embryos from inbred and outbred strains, leading to permanently genetically modified animals.

Oct 28, 2009 · Here we describe the use of zinc-finger nucleases to produce heritable, targeted mutations in the rat by combining in vitro transcription of ZFN-encoding nucleic acids, testing in cultured rat cells, and delivery to the one-cell embryo …

Jul 9, 2014 · Here, we demonstrate the generation of Dmd-mutated rats using a clustered interspaced short palindromic repeats (CRISPR)/Cas system, an RNA-based genome engineering technique that is also adaptive to rats. We simultaneously targeted two exons in the rat Dmd gene, which resulted in the absence of Dystrophin expression in the F0 generation.

Jan 14, 2007 · Here we report the successful generation of insertional mutant rats using the Sleeping Beauty (SB) transposon system. This would benefit a variety of biomedical research fields for which the...

Jun 8, 2007 · Here we show that a tyrosinase-tagged Sleeping Beauty transposon can be used as a simple, efficient method to generate rat mutants in vivo. By making two lines of transgenic rats, one carrying the transposon and another expressing the transposase in germ cells, we are able to obtain bigenic males in which transposition occurs in the germ cells.

In this review, I provide an overview the development of rat genome resources and describe examples of positional cloning in rats in which novel gene functions have been identified. Keywords: disease model; forward genetics; mutation; positional cloning; rat.