These F2 (second filial generation) hybrid mice are the offspring of an F1 x F1 mating, itself the product of a cross between C57BL/6J females (B6) and 129S1/SvImJ males (129S). F2 hybrid mice are genetically unique containing a mix of each parental strain, but in random configuration. F2 hybrids are used to map traits and as approximate controls for genetically engineered strains that were generated with 129-derived embryonic stem cells and maintained on a mixed B6;129 background.

In 2019-2020, researchers at The Jackson Laboratory discovered the 129S1/SvImJ inbred strain (Stock No. 002448) has the Trem2^S148E allele - a naturally occurring variant at position 48351151-48351152 on Chr 17 (rs108080490 and rs107649577; Ensembl GRCm38.p6). This TC to GA transition results in a serine to glutamic acid substitution at amino acid 148 (S148E). This may affect some of these mice.