Designating genotypes: What does '+' really mean?

In many of our JAX presentations and webinars, we discuss rules and nuances of strain and gene nomenclature extensively, but very little mention is made of how genotypes of individual animals should be designated/symbolized. In this post, I would like to correct this oversight.

As far as I know, there are no committee-sanctioned rules that apply to designating mouse genotypes. Those that I describe below, therefore, are just those that I and my colleagues in the JAX Technical Information Services (TIS) group typically use when discussing our mice. (WARNING! I don’t promise you that our genotype designations will make perfect sense, only that I will explain them!)

First, we always use the “+” symbol to indicate a wildtype or unmodified allele, regardless of the kind of strain that is being described. For spontaneously or targeted mutant mice, this notation makes perfect sense: “+” indicates the wildtype allele, and “-” the mutant allele. Thus, we designate our mouse genotypes “-/-” for homozygous mutants, “+/-” for heterozygotes, and “+/+” for wildtypes. Pretty straightforward, so far, I think.

For loxP-containing conditional and “knockin” targeted mutations, the mutant allele is often designated using, “floxed, “flox,” or “fl” for the former, and an abbreviation for whatever sequence is knocked-in to the locus (e.g. cre, lacZ, EGFP, etc.) for the latter; hence the genotypes for homozygotes and heterozygotes become, for example, “fl/fl” and “fl/+” or “cre/cre” and “cre/+”, respectively.

With transgenic mice, we use a slightly different convention. Many investigators use “+” to designate a transgenic allele. This convention makes good sense when discussing “+/-” hemizygotes, but homozygous transgenic mice then become “+/+,” which creates confusion for those of us who typically use “+/+” to indicate a wildtype mouse. This convention also forces wildtype mice to be designated “-/-,” which, of course, is counter-intuitive to folks who use “-” to designate a mutant allele.

To avoid such confusion, the JAX Technical Information Services group typically uses “Tg” to designate transgenic alleles. This allow us to use “Tg/Tg” to indicate homozygous transgenic mice and to still use “+/+” to designate the non-transgenic, wildtype mouse. It follows, then, that we must use “Tg/+” to designate hemizygous transgenic mice, right? Well, actually, no. Because transgenes are extra bits of DNA in the mouse genome that have no corresponding “wildtype” sequence in the unmodified genome, we write the genotypes of hemizygous mice as “Tg/0.″ This convention, we think, helps to avoid the tendency to interpret “+/+” as mice that are homozygous for the transgene. Why, then, don’t we use “0/0″ to indicate the wildtype allele? Well, like I said, we always use “+/+” to designate a “wildtype” mouse, and we think that the “0/0″ designation is too unconventional for many mouse researchers, especially for beginners.

As I stated earlier, there are no hard and fast rules for designating mouse genotypes, and you are free to choose whatever conventions that you like. Whichever terms you use to designate your genotypes, I encourage you to provide some key or frame of reference so that investigators who read your papers and co-workers who have to read your animals’ cage cards can easily identify which genotypes are which. If any of you use other conventions, I’d love to hear about them!