Streptozotocin (STZ) has been widely used to induce diabetes in rodents. Strain-dependent variation in susceptibility to STZ has been reported; however, the gene(s) responsible for STZ susceptibility has not been identified. Here, we utilized the A/J-11 consomic strain and a set of chromosome 11 (Chr. 11) congenic strains developed from A/J-11 to identify a candidate STZ-induced diabetes susceptibility gene. The A/J strain exhibited significantly higher susceptibility to STZ-induced diabetes than the A/J-11 strain, confirming the existence of a susceptibility locus on Chr. 11. We named this locus Stzds1 (STZ-induced diabetes susceptibility 1). Congenic mapping using the Chr. 11 congenic strains indicated that the Stzds1 locus was located between D11Mit163 (27.72 Mb) and D11Mit51 (36.39 Mb). The Mpg gene, which encodes N-methylpurine DNA glycosylase (MPG), a ubiquitous DNA repair enzyme responsible for the removal of alkylated base lesions in DNA, is located within the Stzds1 region. There is a close relationship between DNA alkylation at an early stage of STZ action and the function of MPG. A Sanger sequence analysis of the Mpg gene revealed five polymorphic sites in the A/J genome. One variant, p.Ala132Ser, was located in a highly conserved region among rodent species and in the minimal region for retained enzyme activity of MPG. It is likely that structural alteration of MPG caused by the p.Ala132Ser mutation elicits increased recognition and excision of alkylated base lesions in DNA by STZ.
Mice with dominant white spotting occurred spontaneously in the
C3.NSY-(D11Mit74-D11Mit229) strain. Linkage analysis indicated that the
locus for white spotting was located in the vicinity of the Pax3 gene on
chromosome 1. Crosses of white-spotted mice showed that homozygosity for the mutation
caused tail and limb abnormalities and embryonic lethality as a result of exencephaly;
these phenotypes were analogous to those found in other Pax3 mutants.
Sequence analysis identified a missense point mutation (c.101G>A) in exon 2 of
Pax3 that resulted in a methionine to isoleucine conversion at amino
acid 62 of the PAX3 protein. This mutation site was located in the N-terminal HTH
(helix-turn-helix) motif of the paired domain of Pax3, which is necessary
for binding to DNA and is highly conserved in vertebrate species. Alteration of DNA
binding affinity was responsible for embryonic lethality in homozygotes and white spotting
in heterozygotes. We named the mutant allele as Pax3Sp-Nag.
The C3H/HeN-Pax3Sp-Nag strain may be useful for analyzing the
function of Pax3 as a new model of the human disease, Waardenburg
Syndrome.
One of the most graceful phenomena widely observed in nature is self-reconfiguration; living systems spontaneously reconfigure their body structure through the developmental process. While this remarkable phenomenon still remains much to be understood in biology, the concept of self-reconfiguration becomes undeniably indispensable also in artificial systems as they increase in size and complexity. Based on this consideration, this paper discusses the realization of self-reconfiguration with the use of a modular robot. The main contributions of this paper are twofold: the first concerns the exploitation of emergent phenomena stemming from the carefully designed interaction between the control and mechanical systems; the second is related to the implementation of different inter-modular adhesiveness derived from an artificial cell-differentiation. Here, form generation by self-reconfiguration is considered as the result of time evolution toward the most dynamically stable state. Preliminary simulation results show that stable self-reconfiguration is achieved irrespective of the initial positional relationship among the modules.
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