The derivation of highly germline-competent embryonic stem cells containing NOD-derived genome.
It would be extremely advantageous to the analysis of disease mechanisms in the spontaneous mouse model of type 1 diabetes, the nonobese diabetic (NOD) strain, if genes in this strain could be modified in vivo using embryonic stem (ES) cells and homologous recombination. However, a NOD ES cell line with adequate germline transmission has not yet been reported. We report the development of highly germline-competent ES cell lines from the F1 hybrid of NOD and 129 for use in NOD gene targeting. Consequently, we developed ES cell lines derived from (NOD x 129)F1 x 129 backcross 1 mice, which were intercrossed to select for homozygosity of particular regions of NOD genome known to contain disease loci.
Brook
Frances A
FA
Department of Zoology, University of Oxford, Oxford, U.K. frances.brook@zoo.ox.ac.uk
Evans
Edward P
EP
Lord
Christopher J
CJ
Lyons
Paul A
PA
Rainbow
Daniel B
DB
Howlett
Sarah K
SK
Wicker
Linda S
LS
Todd
John A
JA
Gardner
Richard L
RL
D000818:Animals; D002460:Cell Line; D002678:Chimera; D004622:Embryo, Mammalian / Q000166:cytology*; D005260:Female; D016678:Genome; D018095:Germ-Line Mutation; D006720:Homozygote; D006824:Hybridization, Genetic; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics*; D008815:Mice, Inbred Strains / Q000235:genetics*; D013234:Stem Cells / Q000502:physiology*