A model mouse for any human disease helps to elucidate the pathogenic mechanism and to develop a therapeutic application(s). Therefore, many model mice have been developed. IMPC have been in progress to phenotype KO mouse strains established by IKMC. In this international efforts, the genetic background was unified in C57BL/6N focusing on monogenic traits and diseases. Recently, the genome editing technologies, in particular, the CRISPR/Cas9 system, have made it possible to quickly introduce mutations to a few target loci in a single strain. The genetic studies of polygenic traits and disorders such as mental diseases, metabolic syndromes and life-style related diseases are, however, still limited. We have made RIKEN ENU Mutant Mouse Library of 10,000 G1 males open to public since 2002 and many users have already used and reported their outcomes. Each G1 mouse has ~5,000 mutations; thus, it is plausible to exhibit some polygenic traits due to the interaction among the thousands of mutations. Two such cases have been indeed suggested by users. In order to assess what a part of thousands of mutations interact each other in each G1 strain, we are now conducting systematic QTL analysis focusing on the body weight. Firstly, two outlier G1 strains, G1DB012260 and G1DB008748, for body weight were chosen from the 10,000 G1 Library and revived them by IVF/ET method. We have obtained 81 and 51 G2 progenies and their intercross have given rise to 72 and 128 G3 mice so far from G1DB012260 and G1DB012260, respectively. The 8-weeks-old body weight of the G3 populations showed an increase of genetic variance comparing to the control population, which indicates the existence of some genetic interaction among induced mutations. At the same time, Whole Exome Sequencing (WES) and SNV calls of the two G1 genomes identified 159 and 182 ENU-induced mutations and the genotyping of identified mutations in G3 mice were conducted. The preliminary results of QTL analysis based on the body weight and genotyping of the G3 populations also showed several interactive peaks. We thus encourage users to apply the RIKEN Mutant Mouse Library not only for the monogenic analyses but also multigenic/polygenic studies to establish models for various complex traits and diseases. We have so far identified 944 ENU-induced mutations in 428 target regions based on user’s requests. In addition, WES has catalogued 4801 ENU-induced mutations in 53 G1 strains. A total of the 5,745 mutations are also open to public.