New murine polymorphisms detected by random amplified polymorphic DNA (RAPD) PCR and mapped by use of recombinant inbred strains

Oligonucleotide primers of random sequence that were 12 bases in length, 58% in GC content, and lacking internal palindromes were designed. By random amplified polymorphic DNA (RAPD) PCR, these primers were used to survey for DNA variations between the progenitors of the mouse AXB and BXA recombinant inbred sets (A/J and C57BL/6J). We identified 17 DNA variants detected by 10 primers. Map positions for these variants were determined by comparing their strain distribution patterns in the AXB, BXA recombinant inbred sets with strain distribution patterns of previously published loci. When necessary, BXD and NXSM recombinant inbred sets were also used. These 17 new loci mapped to 12 chromosomes. The 10 primers were also used to survey 20 inbred mouse strains including the progenitors of other recombinant inbred sets and four mouse strains recently inbred from the wild (CAST/Ei, MOLF/Ei, PERA/Ei, and SPRET/Ei).     

Genetic analysis of mortality in murine angiostrongyliasis costaricensis using SMXA recombinant inbred mouse strains

The SMXA recombinant inbred mouse strain set was produced by systematic inbreeding from the F2 generation of a cross between two progenitor inbred strains, A/J and SM/J, which differed markedly with respect to the patterns of infection with Angiostrongylus costaricensis. We have applied this set to genetic analysis of mouse susceptibility to this nematode infection. The mortality was variable among substrains of the SMXA RI strains, indicating the involvement of multiple genes. Linkage analysis showed several chromosomal regions closely linked to mortality; chromosome 6 (D6Rik86, 87; P0.001), 10 (D10Rik66–D10Mit12; P=0.0058), 13 (D13Rik79, 80; P=0.0096) and 17 (D17Mit28–D17Rik76; P=0.0088).     

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.     

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.     

AKXD recombinant inbred strains: models for studying the molecular genetic basis of murine lymphomas.

We analyzed the lymphoma susceptibility of 13 AKXD recombinant inbred mouse strains derived from AKR/J, a highly lymphomatous strain, and DBA/2J, a weakly lymphomatous strain. Of the 13 strains used, 12 showed a high incidence of lymphoma development. However, the average age at onset of lymphoma varied considerably among the different AKXD strains, suggesting that they have segregated several loci that affect lymphoma susceptibility. A relatively unambiguous classification of lymphomas was made possible by using histopathology in addition to detailed molecular characterization of rearrangements in immunoglobulin heavy and kappa light genes and in T-cell receptor beta-chain genes. Among the 12 highly lymphomatous strains, only 2 were identified that, like the parental AKR/J strain, died primarily of T-cell lymphomas. Three strains died primarily of B-cell lymphomas, and one strain primarily of myeloid lymphomas. Six strains were susceptible to both T-cell and B-cell lymphomas. Thus, these strains have segregated genes that affect both lymphoma susceptibility and lymphoma type and should prove to be useful models for studying the molecular genetic basis of murine lymphomas.     

The response of recombinant inbred strains of mice to bacterial lipopolysaccharides.

Fourteen recombinant inbred strains of mice have been produced by the inbreeding of the F2 generation of a cross between C57BL/6J and C3H/HeJ progenitor mice. The responses of these BXH strains to bacterial lipopolysaccharides (LPS) have been characterized. Four BXH strains are high LPS responders and nine strains are low LPS responders. One BXH strain shows intermediate responsiveness which may reflect residual heterozygosity. F1 hybrid mice from low x high responder strains were intermediate in their response to LPS suggesting additive genetic control. The LPS responses in backcross mice from the F1 x low LPS responders showed segregation consistent with LPS responsiveness being determined by a single gene. In 13/14 BXH strains, there was concordant inheritance of LPS responsiveness and the major urinary protein locus Mup-1b. The association of the expression of the Mup-1 alleles with LPS responsiveness in the BXH strains suggests that the defective LPS response gene in C3H/HeJ mice is located on chromosome 4.     

Improved strain distribution patterns of SMXA recombinant inbred strains by microsatellite markers.

To develop SMXA recombinant inbred (RI) strains as more valuable genetic resources, 302 microsatellite (Mit) loci were added to the strain distribution patterns (SDP) reported previously. The improved SDP were constructed in a total of 1085 loci containing 484 Mit markers, 571 restriction landmark genomic scanning (RLGS) spot markers and 30 others. This substantially improved SDP can be freely accessed on our homepage (http://www.med.nagoya-u.ac.jp/sisetu/SDP.htm).