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T H Roderick

Publications and source records attributed to T H Roderick.

89 records · Page 5Linked to original sources
PubMed1970

Two radiation-induced chromosomal inversions in mice (Mus musculus).

Whole-body x-irradiation of male mice has produced presumptive paracentric inversions in 15 animals, as evidenced by high frequencies of first meiotic anaphase bridges. Two of the highest frequencies observed have been propagated through several generations and found to behave as dominant genes. Acentric fragments were observed associated with about 10% of the bridges. The first inversion, in linkage group XIII, has been designated In(13)1Rk, and the second, in linkage group XVII, In(17)2Rk. For In(13)1Rk, recombination was reduced between loci inside and outside the inverted segment.

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PubMedDate not supplied

Mouse chromosome fragility.

When cultures of fibroblast-like cells from inbred mouse strains RBC/Dn and AEJ/GnRk were exposed to 5-fluorodeoxyuridine (FUdR), non-random strain-specific distributions of chromosome gaps, breaks and exchanges were observed. Throughout the genomes there appeared to be specific sites at which lesions occurred preferentially. Two strain-specific fragile sites were identified in strain RBC/Dn at G-band 15A2, and at G-band 19B in strain AEJ/GnRk. Constitutive fragile sites at G-bands 12A2 and 18A2 were identified in both strains. A strain-specific marker at G-band 9B was found in strain AEJ/GnRk. The fragile sites reported here provide an animal model for the study of chromosome fragility as well as polymorphic markers for linkage studies.

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PubMedDate not supplied

Selection for maximum longevity in mice.

In both mice and men, during the adult life span, aging causes an exponential increase in vulnerability to almost all pathologies. Thus, aging is a serious public health problem. Altering the basic mechanisms that control normal aging would be a powerful approach to reduce damage from aging processes, so research identifying these mechanisms is of vital importance. Because life spans are determined by the first biological system to malfunction, it is likely that basic mechanisms are involved in life span extension of animals already having maximum normal life spans for the species. When life spans of a species are extended, all biological systems must function for unusually long times. If there are a limited number of genes for basic mechanisms that control aging rates in multiple biological systems, then life spans can be extended relatively easily. If not, extending maximum life spans would require changes in impractically large numbers of genes, all genes involved in functional life spans of every biological system. In fact, life spans appear to increase rapidly during evolution, suggesting that changes in only a few genes are required. These genes are likely to control underlying mechanisms timing aging in multiple biological systems. The purpose of selection for increased life span is to identify these genes. An important potential problem is that all species have many defective genetic alleles that can cause early disease and death. Selection studies must be designed to distinguish between altering basic mechanisms of aging, and simply avoiding early pathologies due to defective alleles. Animal models that are short lived for their species should be avoided, because their deaths almost always result from genetic defects unrelated to mechanisms of normal aging. During selection, alleles not causing early pathologies may appear to increase life spans by replacing defective alleles in genetic regions linked to early pathologies; however, these affect early disease, not basic mechanisms of aging. A more subtle potential problem is that caloric restriction increases life spans in mice. Selection for long lived mice should focus on more basic mechanisms than breeding mice that voluntarily consume fewer calories. The fact that aging rates in different biological systems are not necessarily coordinated in different individuals suggests that normal aging is timed by more than one mechanism. Thus, the objective in selection for maximum longevity is to capture the entire set of alleles that increase longevity in a species. Wild populations are not practical to use, despite some theoretical advantages, as genes retarding aging would be confounded with those reducing the stress of captivity. Currently we use four-way crosses of inbred strains that represent maximal genetic diversity. Genetic regions important in increasing longevity will be identified using microsatellite markers distinguishing each of the four starting strains over the entire genome. Other genetic techniques proven useful for studying characteristics that are quantitatively controlled by multiple genes may also be useful in studying mechanisms timing aging; these techniques include diallele crosses, recombinant inbred lines, bilineal congenic lines and correlated genetic markers.

Aging↗
PubMedDate not supplied

The hairy ears (Eh) mutation is closely associated with a chromosomal rearrangement in mouse chromosome 15.

The mouse mutation hairy ears (Eh) originated in a neutron irradiation experiment at Oak Ridge National Laboratory. Subsequent linkage studies with Eh and other loci on Chr 15 suggested that it is associated with a chromosomal rearrangement that inhibits recombination since it shows tight linkage with several loci occupying the region extending from congenital goiter (cog) distal to caracul (Ca). We report here (1) linkage experiments confirming this effect on recombination and (2) meiotic and mitotic cytological studies that confirm the presence of a chromosomal rearrangement. The data are consistent with the hypothesis of a paracentric inversion in the distal half of Chr 15. The effect of the inversion extends over a minimum of 30 cM, taking into account the genetic data and the cytologically determined chromosomal involvement extending to the region of the telomere.

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