The AXB and BXA set of recombinant inbred mouse strains

The recombinant inbred (RI) set of strains, AXB and BXA, derived from C57BL/6J and A/J, originally constructed and maintained at the University of California/San Diego, have been imported into The Jackson Laboratory and are now in the 29th to 59th generation of brother-sister matings. Genetic quality control testing with 45 proviral and 11 biochemical markers previously typed in this RI set indicated that five strains had been genetically contaminated sometime in the past, so these strains have been discarded. The correct and complete strain distribution patterns for 56 genetic markers are reported for the remaining RI strain set, which consists of 31 living strains and 8 extinct strains for which DNA is available. Two additional strains, AXB 12 and BXA 17, are living and may be added to the set pending further tests of genetic purity. The progenitors of this RI set differ in susceptibility to 27 infectious diseases as well as atherosclerosis, obesity, diabetes, cancer, cleft palate, and hydrocephalus. Thus, the AXB and BXA set of RI strains will be useful in the genetic analysis of several complex diseases.     

Parental genetic contributions in the AXB and BXA recombinant inbred mouse strains

Recombinant inbred (RI) strains are a valuable tool in mouse genetics to rapidly map the location of a new locus. Because RI strains have been typed for hundreds of genetic markers, the genotypes of individual strains within an RI set can be examined to identify specific strain(s) containing the desired region(s) of interest (e.g., one or more quantitative trait loci, QTLs) for subsequent phenotype testing. Specific RI strains might also be identified for use as progenitors in the construction of consomic (chromosome substitution strains or CSSs) or congenic lines or for use in the RI strain test (RIST). To quickly identify the genetic contributions of the parental A/J (A) and C57BL/6J (B) strains, we have generated chromosome maps for each commercially available AXB and BXA RI strain, in which the genetic loci are colorcoded to signify the parent of origin. To further assist in strain selection for further breeding schemes, the percentages of A and B parental contributions were calculated, based on the total number of typed markers in the database for each strain. With these data, one can rapidly select the RI strain(s) carrying the desired donor and recipient strain region(s). Because points of recombination are known, starting with RI mice to generate CSSs or congenic lines immediately reduces genomewide screening to those donor-strain regions not already homozygous in the recipient strain. Two examples are presented to demonstrate potential uses of the generated chromosome maps: to select RI strains to construct congenic lines and to perform an RIST forAliq1, a QTL linked to ozone-induced acute lung injury survival.     

IRILmap: linkage map distance correction for intermated recombinant inbred lines/advanced recombinant inbred strains

Intermated Recombinant Inbred Lines (IRILs) in plants, or Advanced Recombinant Inbred Strains in animals, are constructed by carrying out generations of intermating between F2 individuals before starting recurrent inbreeding generations by selfing or sib-mating. IRILs are powerful for high-resolution genetic mapping because they have undergone more recombination than usual Recombinant Inbred Lines (RILs). However, there is no mapping software able to generate actual centiMorgan distances from the segregation data obtained with IRILs. IRILmap software converts genetic distances computed with any linkage mapping program designed for RILs, so that IRIL-derived data can be used to get actual centiMorgan distances, directly comparable to F2, backcross or RIL-derived maps.     

A genetic linkage map of the rat derived from recombinant inbred strains

We have constructed a genetic linkage map in the rat by analyzing the strain distribution patterns of 500 genetic markers in a large set of recombinant inbred strains derived from the spontaneously hypertensive rat and the Brown-Norway rat (HXB and BXH recombinant inbred strains). 454 of the markers could be assigned to specific chromosomes, and the amount of genome covered by the mapped markers was estimated to be 1151 centimorgans. By including a variety of morphologic, biochemical, immunogenetic, and molecular markers, the current map integrates and extends existing linkage data and should facilitate rat gene mapping and genetic studies of hypertension and other complex phenotypes of interest in the HXB and BXH recombinant inbred strains. Received: 21 June 1995 / Accepted: 11 September 1995     

Strain distribution pattern in AXB and BXA recombinant inbred strains for loci on murine Chromosomes 10, 13, 17, and 18

Strain distribution patterns (SDPs) of selected loci previously mapped to murine Chromosomes (Chrs) 10, 13, 17, and 18 are reported for the AXB, BXA recombinant inbred (RI) strain set derived from the progenitor strains A/J (A) and C57BL/6J (B). The loci included the simple sequence length polymorphisms (D10Nds1, D10Mit2, D10Mit10, D10Mit14, D13Mit3, D13Nds1, D13Mit10, D13Mit13, D13Mit7, D13Mit11, D17Mit18, D17Mit10, D17Mit20, D17Mit3, D17Mit2, D18Mit17, D18Mit9, and D18Mit4), the restriction fragment length polymorphisms Pdea and Csfmr, and the biochemical marker AS-1. These loci were chosen because they map to genomic regions that had few or no genetic markers in the AXB, BXA RI set. Several of these loci also were typed in backcross progeny of matings of the (AXB)F₁ to strain A or B. The strain distribution patterns for chromosomes 10, 13, 17, and 18 are reported, and the gene order and map distances determined from the backcross data. The addition of these markers to the AXB, BXA RI strain set increases the genomic region over which linkage for new markers can be detected.     

Alcohol preference in AXB/BXA recombinant inbred mice: gender differences and gender-specific quantitative trait loci

The purpose of the present study was to characterize the C57BL/6J, A/J, and AXB/BXA Recombinant Inbred (RI) strains of mice for voluntary alcohol consumption. Quantitative Trait Locus (QTL) analysis was used to provide provisional location of QTLs for alcohol consumption. The inbred strains were screened for levels of alcohol intake (calculated as alcohol preference and absolute alcohol consumption) by receiving 4 days of forced exposure to a 10% (wt/vol) solution of alcohol, followed by 3 weeks of free choice between water and 10% alcohol. A wide and continuous distribution of values for alcohol consumption and preference was obtained in the AXB/BXA RI strains, confirming polygenic influences on alcohol-related behaviors. Significant gender differences were found for both alcohol preference [F_28,651= 2.12, p < 0.001] and absolute alcohol consumption [F_28,647= 2.57, p < 0.001]. In males, putative QTLs were mapped to chromosomes (Chrs) 2, 5, 7, 10, 11, and 16. Multiple regression analysis indicated that approximately 75% of the genetic variance in alcohol preference in males could be accounted for by three of the QTL regions. Several of the putative QTLs appeared to be male-specific (Tyr on Chr 7; D10Mit126 on Chr 10; D11Mit61 on Chr 11). In females, seven putative QTLs were mapped to Chrs 2, 4, 5, 7, 11, 16, and 19. Approximately 90% of the genetic variance in alcohol preference in females could be accounted for by four QTL regions, as determined by multiple regression. The QTL on Chr 11 near D11Mit35 appeared to be female-specific. This site was close to a female-specific QTL (Alcp2) previously mapped in C57BL/6J × DBA/2J backcrosses by Melo and coworkers (Nat Genet 13, 147, 1996). The QTLs mapped for alcohol preference in the present study must be considered suggestive at the present time, since only D2Mit74 met very strict statistical criteria for significance. However, the concordance across several studies for the loci on Chrs 2, 4, 7, 9, and 11 suggest that some common QTLs influencing alcohol preference have been identified. Confirmation of QTLs mapped in the present study is currently being conducted in a new series of recombinant congenic (RC) strains developed from reciprocal backcrosses between the A/J and C57BL/6J progenitors. The concomitant use of both RI and RC strains developed from the same progenitors should provide a powerful means of detecting, confirming, and mapping QTLs for alcohol-related traits. Received: 25 August 1998 / Accepted: 8 October 1998     

Typing recombinant inbred mouse strains for microsatellite markers

In total, 41 different microsatellite variants have been typed in one or more of four different sets of recombinant inbred (RI) mouse strains. Microsatellite variants were selected that were located in chromosomal regions previously lacking markers. These markers extend the regions swept in these RI strains.     

The map expansion obtained with recombinant inbred strains and intermated recombinant inbred populations for finite generation designs

The generation of special crosses between different inbred lines such as recombinant inbred strains (RIS) and intermated recombinant inbred populations (IRIP) is being used to improve the power of QTL detection techniques, in particular fine mapping. These approaches acknowledge the fact that recombination of linked loci increases with every generation, caused by the accumulation of crossovers appearing between the loci at each meiosis. This leads to an expansion of the map distance between the loci. While the amount of the map expansion of RIS and IRIP is known for infinite inbred generations, it is not known for finite numbers of generations. This gap was closed here. Since the recursive evaluation of the map expansion factors turned out to be complex, a useful approximation was derived.     

Use of recombinant inbred strains to map genes of aging

Recombinant inbred strains have been used in a number of organisms for segregation and linkage analysis of quantitative traits. One major advantage of the recombinant inbred (RI) methodology is that the genetic identity of individuals within a strain permits replicate measures of the same recombinant genotype. Such replicability is important for traits such as aging inDrosophila, where phenotypic expression is highly influenced by different environmental conditions. RI strain methodology has an added advantage for DNA marker-based linkage analysis of traits measured over the lifespan of the organism. The DNA can be extracted from individuals of the same genotype as those measured in a longevity study. In this paper an argument is presented for the use of a set of recombinant inbred strains to map the quantitative trait loci involved in the aging process inDrosophila. A unique use of a set of stable, transposable moleular markers to trace the quantitative trait loci involved is suggested.     

Analysis of the mouseAmy locus in recombinant inbred mouse strains

Pancreatic and salivary amylase cDNA probes have been used to search for new DNA fragment length variation among a total of 43 inbred mouse strains. Fragment length differences found with three restriction endonucleases grouped the strains into two major classes. The segregation of these variant fragments has been analyzed among several sets of recombinant inbred strains and is presented here. Previously reported differences for strains YBR and CE have been confirmed. New segregation data for carbonic anhydrase, a locus near the proximal end of mouse chromosome 3, are presented.     

Confidence limits for estimates of gene linkage based on analysis of recombinant inbred strains

Recombinant inbred (RI) strains are extremely useful for genetic mapping. This paper presents a simple method for determining confidence intervals for linkage estimates based on analysis of RI strains. The results show that such confidence intervals are usually large with the currently available numbers of RI strains. Therefore, map positions based only on analysis of RI strains should be interpreted with caution. To facilitate interpretation of linkage data derived from RI strains, a table is presented giving the 95 percent and 99 percent confidence intervals for all possible linkages detected with up to 45 RI strains.     

Genetics of body weight in the LXS recombinant inbred mouse strains

This is the first phenotypic analysis of 75 new recombinant inbred (RI) strains derived from ILS and ISS progenitors. We analyzed body weight in two independent cohorts of female mice at various ages and in males at 60 days. Body weight is a complex trait which has been mapped in numerous crosses in rodents. The LXS RI strains displayed a large range of weights, transgressing those of the inbred progenitors, supporting the utility of this large panel for mapping traits not selected in the progenitors. Numerous QTLs for body weight mapped in single- and multilocus scans. We assessed replication between these and previously reported QTLs based on overlapping confidence intervals of published QTLs for body weight at 60 days and used meta-analyses to determine combined p values for three QTL regions located on Chromosomes 4, 5, and 11. Strain distribution patterns of microsatellite marker genotypes, weight, and other phenotypes are available on WebQTL () and allow genetic mapping of any heritable quantitative phenotype measured in these strains. We report one such analysis, correlating brain and body weights. Large reference panels of RI strains, such as the LXS, are invaluable for identifying genetic correlations, GXE (Gene X Environment) interactions, and replicating previously identified QTLs. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users.