BuiltWithNOF
Derived inbred strains

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There are a number of derivatives of straight inbred strains, and these are  discussed briefly here. They are mostly used in genetical research, but may be useful in other disciplines interested in finding out what genes are  responsible for phenotypic differences between inbred strains. They include the following

Sets of Recombinant Inbred Strains (RIS):
Sets of strains used for identifying and mapping loci which affect a phenotype which differs between two standard inbred strains
Sets of Recombinant Congenic Strains (RCS)
Sets of strains used for identifying and mapping quantitative trait loci which contribute to differences between two inbred strains.
Pairs of Coisogenic Strains
A pair of inbred strains which differ at only a single locus as a result of mutation or (in recent years) genetic modification of a  single locus.
Segregating Inbred Strains
An isogenic strain carrying a mutation and maintained with forced heterozygosity
Pairs of Congenic Strains
A pair of strains which approximate the coisogenic state but produced by ten or more backcrosses of a mutant or GM locus to an inbred genetic background
Sets of Consomic or Chromosome Substitution Strains
Sets of inbred strains which differ from each other by a single chromosome. Useful for studying which genes affecting a trait are situated on each of the chromosomes (if a full set is available).
Conplastic Strains
A pair of strains which differ only in the mitochondrial loci.

References

 

 

 

 

 

 

 

Sets of Recombinant Inbred Strains (RIS):

    Useful for determining whether an observed difference  between the two parental strains is due to a single gene and if so for approximately mapping the gene.

    Recombinant inbred (RI)  strains of mice were first developed by Bailey (1971) and were subsequently developed by Taylor (1976 and later). They are formed by crossing two standard inbred strains, followed by at least 20 generation of b x s mating. Although individual strains may be developed in this way, they are of most value when bred as set of 7-30 or more new strains.

    As an example, Otterness and Weinshilboum (1987) found that the activity of the enzyme Thiopurine methyltransferase differed between strains AKR (low) and DBA/2 (high). A set of 23 recombinant inbred strains had already been bred from a cross between these two strains followed by at least 20 generations of brother x sister mating. When these 23 strains were typed for activity of the enzyme they were fell into two groups as shown in the figure below, with approximately half the strains having high activity and half having low activity. This is the pattern that would be observed if the activity is dependent on a single genetic locus. If the response was dependent on several loci and environmental influences then all levels of activity would be observed.

    The strains had already been typed at the D13Nds1 microsatellite locus. The distribution of this marker among the strains is indicated by the two colours. Blue indicates that the marker in these strains resembled that of the AKR strain, while red indicates that the marker in the strain was like that of DBA/2. There was clearly an association between activity and the D13Nds1 marker, although there were two exceptions. This implies that the gene controlling the enzyme activity was closely linked to, but not identical with, D13Nds1 on chromosome 13.

RIstrains202

    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 Strains

    Useful  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 strains

    Useful 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 strains

    These 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 strains

    Congenic 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 strains

    They 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 strains

    Sets 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.

References

Bailey,D.W. (1971): Recombinant inbred strains, an aid to finding identity, linkage, and function of histocompatibility and other genes.  Transplantation, 11:325-327.
Demant,P. and Hart,A.A.M. (1986): Recombinant congenic strains- a new tool for analyzing genetic traits determined by more than one gene.  Immunogenetics, 24:416-422.
Taylor,B.A. (1976): Development of recombinant inbred lines of mice. Behavior Genetics, 6:118