After establishing a breeding colony utilizing several transgenic males (B6.Cg-Tg(SOD1*G37R)29 Dpr/J aka Line 29) and C56BL/6 females from a commercial source, we noticed that the generated progeny expressed a significant delay in phenotype onset. Typically these animals exhibit an 8-10 months lifespan, but the cohorts in our study survived much longer (transgenic +ve males: median lifespan 600d, transgenic +ve females: 560d). At the outset, male breeders were genotyped (qPCR) by Jackson prior to arrival at our facility. Similarly, at weaning, qPCR analysis was performed to identify transgene positive progeny. The qPCR data indicated that the genomic signatures for all the progeny animals were rather closely clustered, but quite diminished from animals that we had previously derived from a collaborator’s line 29 breeders. Since the dCt values for progeny between breeding pairs were not significantly different, it is highly unlikely that recombination events had resulted in a loss of hSOD1 transgene copies during the 3 breeding cycles that we had performed. At this point, it appears that the most plausible explanation is that transgene copy loss had occurred between the time the animals were deposited at Jackson Laboratory, and by the point that we had obtained these animals for use in deriving our colony. That said, does anyone have any insight with respect to the frequency of transgene instability in the G37R model, or transgenic animal models in general? My survey of the literature has indicated that in the G93A model, this occurs rather infrequently (transgene loss is approximately 3%). I have no reason to believe that it would be more frequent than this, but up until this point, my search has been quite unfruitful.