Altered Monoaminergic Systems and Depressive-like Behavior in Congenic Prion Protein Knock-out Mice.

Beckman et al. (1) reported altered monoaminergic systems and depressive-like behaviors in a line of mice lacking the cellular prion protein PrP (congenic B10.129-Prnp mice). These mice were derived from gene-targeted 129/Ola embryonic stem cells and were subsequently crossed to C57BL/10SnJ mice. Consequently, the genomic region of B10.129-Prnp mice flanking the targeted Prnp locus contains a stretch of up to 47.4Mb isogenic to 129/Ola (2). In this region, any genes polymorphic between the 129/Ola and C57BL/10SnJ strains will display 129/Ola allelotypes (2). This genetic anomaly represents a systematic confounder when congenic knockout mice are compared with wild-type mice of the back-crossing strain, even when using littermates from heterozygous breedings (2). This phenomenon, intrinsic to all congenic knock-outmice, is known as the flanking gene problem.