Substrains may arise for any of the following reasons:
Numerous studies report physiological and behavioral differences among substrains. As examples:
Once a subcolony is determined to be a substrain, it should be given a laboratory code that consists of one to five letters identifying the institute, laboratory or investigator that produced and/or maintains a particular animal strain. Laboratory codes are assigned by the Institute of Laboratory Animal Research (ILAR).
Substrain differences may be particularly important to immunologists, whose studies depend on well-defined, homogenous backgrounds. In fact, immunologists seem to uncover more genotypic variations in inbred strains than do other scientists, perhaps because the molecular traits they often investigate are more sensitive than are other traits to subtle changes (Bailey DW. 1982. Immunology Today 3:210-14).
Reports of actual confounding scientific results due to 129 substrain differences have served as a wake-up call to the research community. The 129 strain originated in 1928 and has since differentiated into numerous substrains. Because embryonic stem (ES) cells derived from 129 mice colonize germlines so efficiently, the 129 strain is one of the most widely used strains in genetic studies. However, for decades ES cell lines from numerous 129 substrains were used with little attention to their differences, in spite of the following problems:
1) The origin and the reported physiological differences between 129 substrains used to be unknown (Hogan B. Beddington R, Costantini F, Lacy E. 1994. Manipulating the mouse embryo: a laboratory manual, 2nd ed. Cold Spring Harbor (NY)).
2) Many loci in the R1 ES cell line appeared to be heterozygous.
In 1997, Threadgill and his colleagues decided to conduct a thorough molecular analysis of the relatedness of various 129 substrains. They found that strain 129/SvJ is significantly different from other 129 substrains and should be more accurately classified as a recombinant congenic strain (129X/Sv) derived from 129/Sv and an unknown strain "X."
Genetic differences between 129 substrains* explained why:
* Petkov and his colleagues (Petkov et al. 2004), using a panel of SNPs, determined that 129X1/SvJ has genetic contributions from C57BL/6J on Chromosomes 5, 7, 14, 18, and 19, and from BALB/cJ on Chromosomes 7, 8, 10, 18, 19, and X, suggesting that the "X" in 129X1/SvJ is an F1 hybrid between C57BL/6J and BALB/cJ.
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