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In-Depth Information
10.3.3.3 Use of the RIKEN Gene-Driven Mutagenesis
Future progress in mouse genetics and functional studies depends on the opening of
ENU-based gene-driven mutagenesis systems to the public and any researchers who
have expertise in analyzing mutant mice. At RIKEN we envision the following
scenario:
1. USER designs the PCR primers for the target gene and sends them to RIKEN.
2. RIKEN screens the mutagenized genomic DNA archive.
3. RIKEN reports all the identified mutations to USER.
4. USER decides which mutation to analyse.
5. RIKEN retrieves live mice from the corresponding frozen sperm and sends
the mice to USER.
6. USER conducts biological and functional studies on the mutant mice as
a bona
fide
biosimulator.
7. The established mutant line will be open to public in an appropriate time.
Based on the above plan, we have already started cooperative feasibility studies
for a number of genes with many collaborators. All information about the current
target genes and their chromosomal locations are open in our website (http://www.
gsc.riken.jp/Mouse/, then see “gene-driven mutagenesis”). As of today, 251 genes
are listed as targets of which 176 genes or 70% are collaborative targets. For each
collaborative gene, we ask USER to be the principal investigator of the study. Using
this cooperative framework we have identified to date about 300 point mutations in
more than 60 target genes.
10.4 Conclusions
Mouse genetics provides a versatile tool to study gene networks and whole genome
function. Here, mutant mice are considered to be
bona fide
biosimulators. Previously,
when geneticists discovered a mutant, it became their life work based on mating and
extensive phenotype analyses. Now, transgenic and knockout mouse systems have
made it possible to alter the mouse genome using DNA technology and embryonic
engineering. Furthermore, ENU mouse mutagenesis projects have opened a new plat-
form for the genomewide study of mouse functional genomics. The renaissance of
classical genetics gave rise to a large number of mutant mouse lines derived from both
phenotype-driven and gene-driven approaches. Prior to this era, more than 5000 mutant
mouse lines were available. Comparable numbers of transgenic and knockout mouse
lines were generated in the past 15 years. Today, ENU mouse mutagenesis contributes
almost 1000 new mutant lines every year. Abundant numbers of mutants as INPUT for
the
bona fide
biosimulator are now available for the development and transformation of
the reproducible high-throughput OUTPUT system as a phenometrics platform.
