Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice

The principal conclusion to be drawn from the foregoing discussion is that the death of cells and the destruction of tissues, organs, and organ systems are programmed as normal morphogenetic events in the development of multicellular organisms. Death in embryonic systems may thus be explored within the same conceptual framework as growth and differentiation. The present exploration has revealed that death during embryogenesis serves utilitarian goals in some instances, at least, that its occurrence is subject to control by factors of the immediate cellular and humoral environment, and that aberrations in its normal pattern of expression provide the mechanism for realization of many mutant phenotypes. Hopefully, it has also pointed toward the appropriate formulation of some of the problems that confront us in understanding the control of death at the level of genetic transcription, the biochemical events which determine and accompany its occurrence, and the pathways of disposition and the developmental significance of disassembled cellular building blocks.

https://science.sciencemag.org/content/sci/154/3749/604.full.pdf

Death in Embryonic Systems

Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses.

The Coat Colors of Mice

Vertebrate cranial placodes I. Embryonic induction.

The recessive gene kreisler (symbol kr ) was discovered by Hertwig (1942 a ), who later described its effects on behaviour (1942 b ) and the inner ear (1944, 1956). She found that it was possible to trace the anomalies of the ear back to 9-day embryos, when the otic vesicle can be seen to be situated in an abnormal position. The present study was aimed at discovering the cause of this abnormality, and at giving a fuller account of the later development of the ear. Material and Methods The particulars of the sectioned material are given in Table 1. Only litter-mate controls were used throughout. The embryos were fixed in Bouin9s fluid, sectioned at 7½ or 10 μ, depending on their age, and stained with Ehrlich9s haematoxylin and eosin. The older material was fixed in Witmaack9s fluid or formalin, sectioned at 10 μ, and stained either the same way or with cresyl violet or Weil9s iron haematoxylin.

The abnormalities of the inner ear in kreisler mice.

Mocha, a New Coat Color and Behavior Mutation on Chromosome 10 of the Mouse

Although the origin of the acoustic ganglion has been the subject of numerous studies there is no unanimity of opinion about it. Most of the earlier investigators (Bartelmez, 1922; Adelman, 1925), using mammalian embryos, believed that it arose from the neural crest, but the experiments of Campenhout (1935) and Yntema (1937) on amphibian embryos led them to the view that it was largely, if not wholly, of placodal origin. This view was supported by Halley (1955), who worked on the cat, and later by Batten (1958), who worked on the sheep. In fact Batten stated categorically that the otic placode was the sole source of the acoustic ganglion. It was thought that an entirely new approach to the problem, namely the use of mutant genes, might help to resolve the difference of opinion. The most suitable mutant for the present purpose seemed to be piebald-lethal (symbol s 1; Lane, 1966).

The neural crest and the acoustic ganglion.

A mutation affecting behaviour occurred in a heterogeneous stock of mice at The Jackson Laboratory in 1956. Genetical tests showed that the mutant gene was semi-dominant with incomplete penetrance, and lethal in the homozygous condition. Further studies established that its effects on the inner ear were different from those of other genes affecting behaviour in a similar manner. It was named ‘dancer’, and assigned the symbol Dc . This paper gives the results of the genetical, anatomical and developmental studies carried out, as well as an account of the phenotypical effects of the dancer gene. The segregation data are given in Table 1. They are based on classification according to behaviour. The results of Dc /+ × Dc /+ matings suggest that the Dc / Dc class dies before classification. This is confirmed by the presence at birth of a distinct inviable phenotype among the offspring of matings of this type.

A new gene affecting the morphogenesis of the vestibular part of the inner ear in the mouse

Deafness associated with locomotor disturbances of labyrinthine origin (head shaking, circular movements) has been known in the mouse for many years, and there are at least ten different gene mutations which produce this syndrome (with or without additional anomalies). Gruneberg (1947) remarked that at first sight it seems remarkable that all the known types of inherited deafness in rodents should be associated with locomotor disturbances. However, shaking and circling are too obvious to be missed, and once detected such mutants will of course be tested for their sense of hearing. Deafness not so ‘labelled’ is unlikely to be discovered in a mouse or rat unless specifically looked for and no such systematic search has so far been made. It is thus quite likely that the absence of ‘uncomplicated’ deafness in rodents is spurious and simply due to the bias against their detection. The fact that there are locomotor disturbances without deafness would seem to support such a suggestion.

M. S. Deol

Papers

The abnormalities of the inner ear in kreisler mice.

Mocha, a New Coat Color and Behavior Mutation on Chromosome 10 of the Mouse

The neural crest and the acoustic ganglion.

A new gene affecting the morphogenesis of the vestibular part of the inner ear in the mouse

A Gene for Uncomplicated Deafness in the Mouse