Pathology of Genetically Engineered and Other Mutant Mice. Группа авторов

and sharing results and resources. This has a huge impact on reproducibility as well as accuracy of interpretation, and is a very important part of making data FAIR (https://en.wikipedia.org/wiki/FAIR_data) as it uses community agreed norms for the exchange and interpretation of information [3].

This chapter provides an overview of the various types of mouse strains (inbred, recombinant inbred, congenic, consomic, hybrid, and others [Table 3.1]), outbred stocks, and mutations (spontaneous or engineered) and how their symbols reflect what they are and how they were made. Methods for creating genetically engineered mice are numerous and rapidly changing [4], so they will not be covered here other than in providing information on the currently used genetic designations for the mice created.

Why Use Standardized Nomenclature?

Even before the days of easy access to computers and search algorithms, words were created to reflect specific things. In medicine, for example Latin was adopted in Europe as a language commonly understood in many countries with their own languages and with defined, agreed meanings – a lingua franca. In so doing, clinicians could communicate reliably with each other through time and across locations. The same is true for mouse genetic nomenclature (Table 3.2). This has become more important when exchanging and aggregating information between international databases to access, analyze, and distribute data. Searches can only be accurately completed when words, or gene and protein symbols, are written correctly and have semantic consistency. Some databases, such as that of the Sanger Mouse Genomes Project (http://www.sanger.ac.uk/sanger/Mouse_SnpViewer), will only work if the correct current gene symbol is entered. If your search returns “The gene you selected is not in the database,” it may mean that you entered the wrong symbol or the name/symbol has been changed and is no longer in use. For example, if you search for p53 in this database, it returns the response above as the correct current term is Trp53 (Figure 3.1).

The Mouse Genome Informatics Database (MGI, www.informatics.jax.org), fortunately, associates synonyms, the unofficial symbols used in publications, with their official nomenclature. Therefore, a search for the commonly used symbol for the gene mutated in publications can be used to find the currently used correct gene and allele symbol. Figure 3.2 illustrates how this can be used to identify the correct allele for Cdx2 in a paper.

International committees were organized to standardize genetic nomenclature for rodents (http://www.informatics.jax.org/mgihome/nomen/short_gene.shtml), humans (https://www.genenames.org/about/guidelines/#!/#tocAnchor‐1‐29), and other species. The MGI database provides detailed information on this subject for mice (http://www.informatics.jax.org/mgihome/nomen/index.shtml) and The Jackson Laboratory also offers a quick guide to nomenclature (https://www.jax.org/jax‐mice‐and‐services/customer‐support/technical‐support/genetics‐and‐nomenclature). This system has been in use and evolving for over 80 years [5]. One goal of these committees is to provide concise, precise, and unique gene symbols and names (Figure 3.3). Mouse genetic nomenclature continues to evolve to accommodate the ever‐increasing complexity of functional genomics as well as the genetically engineered mice created, reflecting the biotechnology that made these advances possible.

Table 3.1 Types of mouse strains.

Inbred mice: 20 generations of brother X sister matings using mice of disparate or even unknown backgrounds

F1 hybrid mice: Progeny of two inbred strains

F2 hybrid mice: Progeny of a female and male of the same F1 hybrid lineage

Recombinant inbred (RI) mice: 20 generations of brother X sister matings from parents of different inbred strains

Recombinant congenic mice: Two inbred strains are crossed followed by several backcrosses to one of the parental strains. The resulting mice are then inbred without selection

Collaborative Cross (CC) mice: Modified RI lines using parents from 8 genetically diverse inbred strains

Congenic mice: Moving a defined genetic interval from one inbred strain to another inbred strain

Consomic mice: A strain in which one intact chromosome from the donor strain is transferred to a host strain (one line is created for each chromosome)

Conplastic mice: Backcrossing the nuclear genome from one inbred strain into the cytoplasm of another inbred strain (mitochondrial parent is always the female parent during the backcross)

Table 3.2 Standardized nomenclature.

AdvantagesProvides a unique identifierStandardizes spelling for accurate retrievalConveys the maker and technology used to create mutations and strainsCan communicate detailed genetic background information

DisadvantagesSometimes complexSometimes incomplete information

UsesPublications (most journals require use of official standardized symbols)Accurate ordering (to make sure that you get what you think you really ordered!)Correct breeding (facilities management)Maintain master pedigree and records

      In the early development of the Mouse Genome Database and MGI (see Chapter 2), italics and Greek letters could not always be used online and be retrieved by different computers, browsers, or software versions. Thus, in many databases, gene symbols are not italicized, and Greek letters are replaced by the modern English alphabet. Periods and commas could not always be visualized on computer screens so commas were replaced by semi‐colons, a critical problem when dealing with congenic strains, as discussed below. Gene names and symbols also changed over time to reflect new discoveries and to more accurately place them in molecular pathways or with genes of similar structure and function. In spite of all of this, MGI constantly maintains the most up‐to‐date nomenclature that can be searched using all previously assigned or published symbols (Figure 3.2). It is important to look for and use the most current symbol as, over time, the same symbol may have been used by different laboratories for many different genes. For example, p38 currently is the synonym for 13 different genes on 10 different chromosomes (Figure 3.3).

      Standardized strain names inform readers of the specific strain type (inbred, hybrid, outbred, etc.), genetic background, source (vendor or research laboratory), and the mutation(s) carried by the mice used in a study. This information is critical for accurate reporting and scientific reproducibility. But where to start and how to understand and use this information? This chapter will discuss basic mouse genetics as it relates to the nomenclature used at the time of writing.