ENU-induced mutation. The mutation comprises a T to C transition that modifies the splice donor sequence of Exon 20, resulting in aberrant mRNA splicing between cryptic splice donors and the normal Exon 21 splice acceptor. cDNA sequence analysis has identified the abnormal splice products: frameshifted mRNAs containing premature translation stop codons that terminate the protein before the DOCK-homology region 2 (DHR2) domain. DHR2 is known to bind to G proteins of the Rho family, promoting GTP -- GDP exchange and initiating a variety of cellular responses.

Homozygous: Defective antibody response to immunization: failure to sustain antibody formation, undergo affinity maturation or to mount heightened recall (memory) response upon booster immunization. DOCK8-mutant B cells were unable to form marginal zone B cells or to persist in germinal centers and undergo affinity maturation. Dock8 mutations disrupted accumulation of the integrin ligand ICAM-1 in the B cell immunological synapse but did not alter other aspects of B cell antigen receptor signaling.

Wild-type littermates

The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.

Chris Goodnow, Ph.D., F.A.A., F.R.S., Australian National University.