Fine mapping of Ath6, a quantitative trait locus for atherosclerosis in mice.

Ath6 is a novel quantitative trait locus associated with differences in susceptibility to atherosclerosis between C57BL/6J (B6) and C57BLKS/J (BKS) inbred mouse strains. Combining data from an intercross and a backcross (1593 meioses) between mice from B6 and BKS strains and from The Jackson Laboratory interspecific backcross panels, (C57BL/6J x Mus spretus) F1 x C57BL/6J and (C57BL/6J x SPRET/Ei) F1 x SPRET/Ei, we constructed a consensus genetic map and narrowed Ath6 to a 1.07 +/- 0.26 cM interval between the anonymous DNA marker D12Pgn4 and the gene Nmyc1. This region is near the proximal end of murine Chromosome (Chr) 12, which is homologous to the human chromosomal region 2p24-p25. Marker order in the Ath6 region was concordant among the two crosses and The Jackson Laboratory interspecific backcross panels. This high resolution map rules out candidate genes encoding apolipoprotein B, syndecan 1, and Adam17. The two Ath6 crosses have a combined potential resolution of 0.06 cM.

Concordance of murine quantitative trait loci for salt-induced hypertension with rat and human loci.

To investigate the genetic control of salt-induced hypertension, we performed a quantitative trait locus analysis on male mice from a reciprocal backcross between the salt-sensitive C57BL/6J and the normotensive A/J inbred mouse strains after they were provided with water containing 1% salt for 2 weeks. Genome-wide scans performed on these mice and analyzed with a combination of conventional marker-based regressions and a novel simultaneous search for pairs revealed six significant quantitative trait loci associated with salt-induced blood pressure, two of which were interacting loci. These six loci, named Bpq1-6 for blood pressure quantitative trait loci, mapped to D1Mit334, D1Mit14, D4Mit164, D5Mit31, D6Mit15, and D15Mit13. Furthermore, five of these six loci were concordant with hypertension loci in rats, and four were concordant with hypertension loci in humans, suggesting that quantitative trait loci mapping in model organisms can be used to guide the search for human blood pressure genes.

An edited linkage map for the AXB and BXA recombinant inbred mouse strains.

We have updated the history of the AXB and BXA recombinant inbred (RI) strains, typed additional loci, and edited the AXB, BXA RI database. Thirteen of the original 51 AXB and BXA RI strains are either extinct or genetically contaminated, leaving 33 living strains available from The Jackson Laboratory. However, we found a high degree of similarity among three sets of strains, indicating that these strains are not independent, which leaves 27 independent RI strains in the set. Accordingly, we modified the database by combining the AXB and BXA RI sets and eliminating strains that were genetically contaminated or extinct with no available DNA. We added 92 newly typed loci, retyped some questionable genotypings, and removed loci with excessive double crossovers or an insufficient number of typed strains. The edited strain distribution pattern (SDP) is available on the World Wide Web (WWW) (http://www. informatics.jax.org/riset.html) and now includes over 700 loci. Each locus is linked to adjacent loci with a LOD score of at least 3.0 with a few described exceptions. We also carried out a second editing designed for the analysis of quantitative trait loci by deleting extinct strains and loci with identical SDPs; this edited database is also available on the WWW.

The cerebellum and initiation of movement: the stretch reflex.

Studies of the stretch reflex in decerebrate cats indicate a phase advance of peak sinusoidal tension in steady-state cycles between 0.1 and 10 Hz. This phase advance is reduced in acute and chronic cerebellectomy, as shown in previous investigations. Also, the augmentation of muscle peak tension in initial sinusoidal stretch cycles at 0.5-5 Hz has been found to be reduced during the time of reflex and motor instability in the several months following cerebellar ablation. This report shows the increased amplitude and phase lead of integrated electromyographic activity in initiating sinusoidal stretch cycles in the decerebrate cat. These reflex aspects are demonstrated in relation to the discharge of neurons in the dorsal spinocerebellar tract and of cerebellar cortical Purkinje cells in initial sinusoidal cycles. The intensity and phase advance of the discharge in dorsal spinocerebellar tract neurons is altered little, but these features are usually increased in Purkinje cells during initial stretches compared to continuous cycling. In terms of overall motor control, these findings are compatible with concepts of movement control, modulated by the cerebellum, in which the discharge of antagonist motor neurons is regulated in concert with that of agonist muscles upon initiation and termination of movement.

Muscle silent period in Parkinson's disease.

The muscle silent period was measured in 11 patients with moderate to severe rigidity associated with Parkinson's disease. The determinations were made under conditions of maximum disability for each patient, since all medications had been withdrawn before testing. The duration of the EMG silence, produced by small and large electrical twitch contractions of the adductor pollicis muscle, fell within a range of values previously determined for normal individuals. Major alleviation of the rigidity and bradykinesia with chronic oral l-dopa therapy was not accompanied by any change in the silent period. It was concluded that in untreated Parkinsonism, and also after its treatment with l-dopa, the functioning of the muscle spindles and local inhibitory reflexes remains normal.