Clinical genetics / edited by Arnold Sorsby.

Date:
1953
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Clinical genetics / edited by Arnold Sorsby. Source: Wellcome Collection.

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    PENETRANCE AND EXPRESSION of fresh rat pituitaries over a period of several weeks. The treated animals resume growth, reaching a practically normal adult size; they mature sexually, and in at least one case a treated male has proven fertile; all of the endocrine abnormalities disappear except that of the anterior pituitary, which remains unaffected by the treatment (Francis, 1944, includes full literature review). The expression of the yellow gene in the mouse is also apparently subject to hormonal modification, although the nature of the effective hormonal factor has not been identified. Mice heterozygous for this gene (homozygotes are inviable), besides being yellow, have a subnormal basal metabolic rate and a tendency toward excessive obesity, often weighing, when adult, twice as much as their non-yellow litter mates. No histologic abnormalities of either thyroid or pituitary have been detected ; nevertheless, if a young yellow mouse is joined in parabiotic union with a normal mouse and cross-circulation becomes estabhshed, neither the yellow nor the normal member of the pair becomes obese ; pigmentation is unaffected (Weitze, 1940). A somewhat comparable eff'ect of parabiosis with a genetically normal animal has been observed in cases of mice homozygous for the jittery gene (De Ome, 1945). Ordinarily these animals develop signs of muscular inco¬ ordination, of rapidly progressive severity, within about two weeks after birth. Slightly later they begin to exhibit convulsions, referred to as tetany by De Ome, although Grüneberg (1947) finds the description more suggestive of epileptic seizures. Growth ceases shortly after the onset of the seizures, which recur with progressively increasing frequency until terminal prostration ensues, followed shortly by death at a mean age of 31 days. Л variety of treatments suggested by the symptomatology and pathology had no discernible effect. In jittery mice parabiosed with normal litter mates shortly after the appearance of first symptoms, however, growth continued at a normal rate, the convulsive seizures were entirely suppressed, and length of life was significantly prolonged, although only to an average age of 51 5 days ; in the meanwhile, the signs of muscular incoordination persisted. Diabetes in man.—Accumulating evidence that diabetes mellitus in man generally develops on the basis of genetic predisposition (Harris, 1949, 1950) makes the affection a good illustration of the possibility of modifying genotype expression by hormone treatment ; in this instance the aetiological implication of other environmental influences is also very probable, as is suggested by the heterogeneity of incidence in different social classes, and by the frequently wide disparity of age of onset in identical twins. The familial occurrence of the rare abnormality, diabetes insipidus, is almost certainly attributable to the segration of a conditionally dominant gene with not quite complete penetrance (which, however, probably accounts for only a minority of non-familial cases), and posterior pituitary preparations are often effective in controlling the manifestation of the gene. Phenocopies Experimental observations The examples of the effects of environmental factors on gene expression have involved particular genes or gene complexes which, when present in animals reared in environments within the normal range, result in phenotypic aberrations. Aberrations simulating the effects of known mutant genes, but produced by the 14