Since this initial proof of concept experiment, numerous groups have continued to advance the field of transgenic mouse models created by CRISPR/Cas9.
Mouse models created via both transgenic and knock-in approaches (Messing et al., 1998; Hagemann et al., 2006; Tanaka et al., 2007) clearly show that simply elevating the level of wild-type GFAP or expressing mutant GFAP leads to the formation of Rosenthal fibres.
The first mouse model created was hypomorphic for the mouse DKC1 homologue, Dkc1, resulting in a four-fold reduction of Dkc1 mRNA expression in males and two-fold in females [54].
In this article, we present a new mouse model, created by using a gene-trap strategy to introduce a transcriptional stop codon to intron 1 of the Ncu-g1 gene (Ncu-g1 gt/gt).
Thus, it is clear that not all mouse models are created equal.
The TgPWS and TgAS mouse models were created by insertion of an LMP2A transgene array of ~80 copies [ 7] that fortuitously generated a deletion equivalent to those that occur in PWS and AS in the human.
Indeed, the observation that BET-BRD inhibitors (e.g., JQ1) effectively block cellular growth through transcriptional repression of c-Myc in mouse models has created the rationale for clinical trials in c-Myc-dependent cancer types (Mertz et al., 2011).
The lack of expert mouse pathologists in academic environments does not seem to have significantly improved in the last 10 years (Sundberg et al., 2004; Adissu et al., 2014), but the number and complexity of mouse models being created continues to expand at an ever-increasing rate.
In addition to the large number of mouse models being created with CRISPR/Cas9 technology, additional organisms have proven responsive to this method of manipulation, including traditional animal models: Drosophila melanogaster [ 73, 74], Caenorhabditis elegans [ 75, 76], Saccharomyces cerevisiae [ 77] and Dani rerio [ 78, 79].
A new Mecp2 'knock-in' mouse model was created based on a first-generation Mecp2-knockout mouse, created by insertion of an 'exogenous' Mecp2 gene [ 38].
S89G-DMP1 knock-in point mutation mouse model was created with homologous recombination method by Beijing Biocytogen Co., Ltd, China.
