|
The RI strains are designated by the names of the two parental strains (usually abbreviated) separated by a capital letter X and a number to distinguish between the different strains of the set, e.g. AXB12 is one of a set of recombinant inbred strains arising from a cross between strains A and C57BL. Reference needs to be made to the strain history to discover exactly which substrains were involved. Individual recombinant inbred strains will have the laboratory registration code appended in the usual way, e.g. AXB12/J if the strain is bred at the Jackson Laboratory. Further details are given on the Jackson Laboratory web site (http://jaxmice.jax.org/info/index.html) Sets of Recombinant Congenic StrainsUseful for identifying and mapping quantitative trait loci (QTLs) They are developed Demant and Hart (1986) by crossing two standard inbred strains, followed by a few (usually 2-3) generations of backcrossing to one of the parental strains (the recipient strain), then b x s mating several strains for the equivalent of about 20 generations, counting each backcross as being equivalent to two generations of b x s mating. Thus, an set of RC strain developed as a result of three backcrosses to one of the inbred parental strains would require 14 generations of b x s mating to qualify as an inbred strain. Sets of these strains offer a way of isolating loci that contribute to variation in characters controlled by many loci. The strategy is to phenotype the full set of strains for characters in which the parental strains differ, with the possibility that most of them are similar to the recipient strains, but a few differ as a result of gene from the donor strain. If the set of strains has been genotyped at many loci, then there is a good chance that the polymorphic loci can be mapped. This is a powerful method because large numbers of animals can be typed, so quite small genetic effects can be detected. RC strains are designated by an upper case abbreviation of the names of the two parental strains, with the recipient strain given first, separated by a lower case "c". Individual strains are numbered without an intervening hyphen, though this may be used if the last strain name is a number, such as strain 129. Thus CcS2 is the second strain in the set of RC strains developed using BALB/c (abbreviated C) using strain STS (abbreviated S) as the donor strain. The number of generations of backcrossing and inbreeding are designated in the usual way. Thus N3F20 would indicate three generations of backcrossing and 20 generations of b x s mating. Coisogenic strainsUseful for studying the effects of a mutation or transgene free of interference from segregation in the genetic background, although the expression of the gene may depend on the background. A pair of substrains are said to be coisogenic when they differ at only a single locus as a result of a mutation which is subsequently be maintained in a separate line (see Chapter 9). Knockout mice which have been developed in an inbred strain as a result of the disruption of a single genetic locus by gene targeting are also coisogenic with the normal parental strain. These are designated by the strain symbol, and where appropriate the substrain symbol, followed by a hyphen and the gene symbol (in italics in printed articles) e.g. DBA/Ha-D. If the gene is maintained in a heterozygous condition a" +" is added to the symbol, followed by a slash, e.g. DW-+/dw would be a strain coisogenic with DW-+/+, carrying the Segregating inbred strainsThese are produced by inbreeding with forced heterozygosity at a particular locus, i.e. by brother sister mating, but using matings like +/+ x +/m or +/m x +/m, where + is the wild type and m is a mutant or variant. A minimum of 20 generations of sib mating are required. The strain is designated in the same way as a coisogenic strain with the strain name followed by the gene symbol, though an indication of the segregating locus is optional. For example, strain DW carries the dwarf mutation, and may be designated DW-+/dw or more simply as DW. Congenic strainsCongenic strains are widely used in research in order to study the effect of a gene without serious complications from a segregating genetic background. These strains are developed by backcrossing a gene to an inbred strain, their "inbred partner" (see chapter 9). They approximate coisogenic status, but differ in that in addition to the locus, they differ from their inbred partner by an associated length of chromosome. A minimum of 10 backcross generations are required, counting the F1 as the first. The number of backcross generations may be indicated by an N, e.g. F23N12F5 would represent a strain inbred for 23 generations followed by 12 generations of backcrossing, then a further five of sib mating. Congenic strains are designated by a compound symbol consisting of the full or abbreviated designation of the inbred partner strain, a period, the full or abbreviated designation of the donor strain, followed by a hyphen and the designation of the differential locus. e.g. B10.129-H12b. This is a strain congenic with C57BL/10 (hence B10), but carrying b allele at the H12 locus donated by strain 129. "Congenic resistant" strains were produced by backcrossing with selection for skin or tumour graft rejection. In such cases the differential locus may not be known at the time that the strain is developed, in which case any symbol is omitted. Many of these strains are now well known by a designation which does not include the gene symbol, e.g. B10.D2 is a congenic resistant strain developed by backcrossing a tumour transplantation resistance gene from DBA/2 to C57BL/10. It is now known that the "factor" that was backcrossed resides in the major histocompatibility (H2) complex. In cases where the donor strain is not relevant or not defined (e.g. if it is a wild mouse), it may be omitted. Many congenic strains carrying mutations are simply known by the strain designation followed by the gene symbol, e.g. C57BL/6J-+/ob is a strain congenic with C57BL/6J, but carrying the obese mutation. In such cases it may not be obvious from the designation whether the mutation occurred within the strain, or whether it was produced by backcrossing to an inbred strain. A list of congenic strains differing at alloantigen loci (i.e. `congenic resistant') is given by Klein, (1973). This gives details of the inbred partner (or recipient) strain, the differential locus, the strain name, the person who produced the congenic strain, the holders, the number of backcross generations and additional remarks. Brief lists are also given in Chapters 13 (mice) and 14 (rats) Consomic or chromosome substitution strainsThey are useful for the rapid identification of which chromosomes carry genes affecting a particular trait. They are produced by backcrossing a whole chromosome such as the X or Y chromosome onto an inbred strain. The designation is HOST-STRAIN-CHROMOSOME DONOR STRAIN. FOR EXAMPLE, C57BL/6J-YAKR represents strain C57BL/6J, but with the Y-chromosome derived from strain AKR as a result of at least 10 generations of backcross matings in which strain C57BL/6 is always the female parent. Conplastic strainsSets of strains which differ only in the mitochondrial DNA. These are developed by backcrossing the nuclear genome from one strain into the cytoplasm of another, i.e. the mitochondria are derived from the donor female and only males from an inbred strain are used in the backcrossing. These are designated as NUCLEAR GENOME-mtCYTOPLASMIC GENOME , e.g. C57BL/6J-mtBALB/c represents strain C57BL/6J, but with the mitochondrial genome derived from strain BALB/c. A minimum of 10 backcross generations are required. ReferencesBailey,D.W. (1971): Recombinant inbred strains, an aid to finding identity, linkage, and function of histocompatibility and other genes. Transplantation, 11:325-327.
|
|||||||||||||||||||||||||||||||||||