John W. Gowen

Determination of sex through genes in a major sex locus in Drosophila Melanogaster 2

HEREDITARY control of sex had first support when unequal chromosomes were shown to be directly correlated with the sex of an individual or its progeny. Over the years no specific sex loci could be located within these chromosomes, however. Polyploid types within Drosophila showed that the sex chromosomes were not the only factors. Sex determination appeared to rest rather on a balance between the sex chromosomes and the autosomes. In Drosophila the X chromosomes operated by pushing the organism toward the female type, the autosomes pressed toward the male type. The Y chromosome had little effect. Loci for major sex genes utilising the intersex types as test agents were sought but again in no clear-cut instance were they found. In the interim major sex genes appeared through observed mutational types. Sturtevant (1920, 1921) in D. simulans isolated a gene in the second chromosome which could convert diploid females to intersexuals, and rendered males sterile. Phenotypically these intersexuals were femalelike in that they lacked sex combs, had 7 dorsal abdominal tergites, ovipositor of abnormal form, 2 spermathece and lacked the penis. They were male-like in having first genital tergite although abnormal in form, lateral anal plates, claspers, black pigmented tip to the abdomen. The gonads were rudimentary. The gene, as was expected since it was recessive, had no effect on D. simulans ymelanogaster hybrids. Lebedeff in Drosophila virilis, studied a recessive gene in the third chromosome which converted diploid females into intersexuals. These intersexuals were arranged on the basis of their morphology from extreme female type with nearly normal female appearance and reproductive organs (ovary undifferentiated) to male type (undeveloped testis and sperm). Between these types numerous hermaphroditic progeny occurred having imperfect but corresponding male and female organs jointly present. Dohzhansky and Spassky (194 i) in Drosophila pseudoobscura observed 2 progenies containing intersexual individuals. These intersexuals were thought to be due to a single dominant gene transforming diploid females. They were characterised by two sets of more or less complete genital ducts and external genitalia but only one pair of gonads. One set of ducts and genitalia was almost always more female-like

CONTRIBUTIONS TO SURVIVAL MADE BY BODY CELLS OF GENETICALLY DIFFERENTIATED STRAINS OF MICE FOLLOWING X-IRRADIATIONS

1. The influence of x-irradiation absorbed in three body regions and in the combinations of these regions has been measured by three subsequent responses: survival to radiation, natural resistance to disease and ability to acquire resistance following contact with the disease agent, S. typhimurium. The effects of irradiation are presented in this paper. Papers on natural and acquired resistance will follow. The experiment was designed as a factorial with five genetically differentiated strains of mice, S, Z, K, Q and Ba; four levels of radiation: 0 r, 320 r, 480 r and 640 r; eight treatment groups and two sexes. All mice were 46 ± 3 days of age when irradiated from a 250 pkv x-ray source operated at 30 ma with 0.25 mm. Cu + 1 mm. A1 filter at a dose rate averaging 170 r/minute. For the initial treatment the strains and sexes were well balanced, at least 50 mice in each of the 25 different treatment groups. The bodies of the mice were marked off in three regions, head h, mid m, and rear r, each comprising ...

Hereditary Differences in Serum Proteins of Normal Mice.

Summary In a study of the serum proteins of 7 mouse strains, it was established that there were inherent differences in the electro-phoretic patterns and in the amount of total serum protein. A distinct β-globulin component was found in only one, E, of the strains. The hybrid progeny of this strain also had this globulin component in their serum. This indicates that the protein is probably determined by a dominant gene (or genes).

EFFECTS OF X-IRRADIATION UPON POSTNATAL GROWTH IN THE MOUSE

1. The effect of x-irradiation of mouse embryos upon their postnatal development was measured by several responses: body weight changes from birth to maturity, lifetime fecundity, and total lifespan. The body weight responses are reported in this paper. Three genetically differentiated inbred strains of mice, Ba, K, and S, and all their possible hybrids, including reciprocals, were used. Pregnant females were exposed to single whole-body 250 pkv x-ray dosages from 20 r to 320 r on 64, 10½, 14½, and 17½ days gestation, as timed from the appearance of a vaginal plug. In addition the study included progeny irradiated on the day of birth without any irradiation of the maternal organism. Postnatal growth was followed from birth to 75 days of age, individuals having been weighed at birth, 12, 26, 40, 60 and 75 days.2. Body weights were adjusted by making use of the pooled regression coefficient of body weight on litter size over all treatments. Body weight response was found to be dependent on both level of irr...

Cortisone and Mortality in Mouse Typhoid. I. Effect of Hormone Dosage and Time of Injection.

Summary Cortisone, administered in single injections ranging from 0.25 to 5 mg, markedly decreased resistance of mice to S. typhimurium. Cortisone had the greatest effect on resistance when administered within 2 days before or after typhoid inoculation. Subcutaneous injections of two other steroids, progesterone and desoxycorticosterone acetate, in dosage range of 0.1 to 10 mg, had no effect on mortality in mouse typhoid.

EXPERIMENTAL ANALYSIS OF GENETIC DETERMINANTS IN RESISTANCE TO INFECTIOUS DISEASE

Problems of infectious disease susceptibility and resistance have been extensively studied by the epidemiologist, the bacteriologist, and the geneticist. The objectives of these scientists, although expressed differently, have much in common. The epidemiologist, chiefly through the study of spontaneous epidemics, seeks to specify the factors that affect the initiation, the spread, and the regression of the disease. The bacteriologist’s considerations are (1) to assign a pathogen as the specific causative agent for the disease and (2) through treatments of this agent to generate means of controlling the disease. The geneticist utilizes both of these approaches as fundamental to his problem but, in addition, directs his attention to the questions of why there should be variations in survival of the hosts that may be exposed to the disease and why comparable variations are observed in pathogen virulence. The plant breeder through the centuries has recognized that some plants of a species were resistant whereas others were susceptible to the same disease. The culmination of this thinking came when Biffen (1905) interpreted the observed resistances and susceptibilities of certain wheat varieties to yellow rust as due to the action of a single gene pair. This observation has been extended to cover a large number of species of plants and their diseases. Resistance to given diseases within a plant species has been shown to be genetically independent or linked with other characteristics. A locus may be occupied by several alleles, whose phenotypes show graded differences in resistance. Resistance, as displayed by the different genetic phenotypes, is specific for particular genetic phenotypes in the pathogen. Physiological forms of the rust organisms in cereals are numerous. A single form of rust may invade a host or be resisted by it according to the presence or absence of a single gene in the host inheritance complex. Two or more different rusts may sometimes be controlled by the presence or absence of a single gene. For other rust genotypes, two or more host loci and their proper genes are necessary for similar control. Pandemics of cereal diseases have been rendered less detrimental by world-wide search for host genes that have specific resistances to different disease types. This hand-and-glove relationship of the host genotypes to the pathogen genotypes is to the liking of the geneticist but has unfortunately seldom appeared in animal material. The all-or-none susceptibility of a given strain or species is seldom approached where the observations are on adequate numbers of individuals. The liver disease of mice intimately associated with the pathogen Bacillus pilijormis is perhaps as near a case in point. Tyzzer (1917) observed species

EFFECTS OF X-IRRADIATION OF MICE EXPOSED IN UTERO DURING DIFFERENT STAGES OF EMBRYOLOGICAL DEVELOPMENT ON DURATION OF MATURE LIFE

1. Mature lifespans, 75 days of age to death, when the mice were exposed to irradiations at different stages of uterine development, showed reductions in mean longevity which were dependent on both x-ray dose and period of embryological cycle. The design for this study was factorial. There were five irradiation treatments, 0, 20, 80, 160 and 320 r, six embryological stages: untreated, 6½, 10½, 14½, 17½ and newborn (19½) days of uterine development, two sexes and nine mouse strains. Three of the inheritance groups were inbred strains and six were the reciprocal crosses of these strains. Efforts were made to obtain two mice for each cell of the design. However, some treatments were so severe that this was impossible. X-ray dosages of 160 and 320 r at embryological ages 6½, 10½ and 14½ days were too lethal to obtain the requisite number of progeny in these groups.2. Six hundred and forty-seven completed mouse lives were collected. Mature lifespan ranged downward from 1194 days for the males and 921 days for ...

A Single-Gene Antagonism Between Mother and Fetus in the Mouse.

Summary A new type of maternal-fetal incompatibility, not involving erythroblastosis, is demonstrated by reciprocal matings in mice. The conditioning factor is a recessive mutant gene named “hair-loss.” Normal-hair progeny of hair-loss mothers are ordinarily born alive but suffer excessive mortality during first 2 weeks, even when fostered by normal mothers. The syndrome consists of inadequate lung inflation, inferior growth, and fragile bones. Mortality is very high when a previous litter was being raised by the mother during pregnancy, but seems otherwise not related to parity.

Genetic patterns in senescence and infection.

The study of ways and means to alleviate the effects of aging in man is indeed important, but such an approach is somewhat removed from the basic question of what precursors are responsible for these changes. Aging is a problem of dynamics in which life and environmental forces are operating both with and against each other. The factors which initiate aging need to be separated frem those which are only the result of aging. Knowledge may be sought by which to control the primary factors and make predictions of their effects before aging happens rather than after it has occurred. There is some hope that this may be achieved by man, since nature has done it. Life spans among species, as well as within species, vary widely. Some Pinaceae may live for 2,000 years, and even then their deaths often are due to man’s axe or to accidental lightning rather than to cellular changes referable to aging. Other species may live but a day. The life spans of different species show all specificities between these known extremes. Similarly, within species, there are differences in survival which are characteristic of the various strains. In 10 genetically different mouse strains, the average life spans range from 368 to 692 days. Many of the differences among the shorterlived or longer-lived groups may be traced to differences in their inheritanceseven in rare cases to single genes as, for instance, annual and biannual clovers. While we are scientifically challenging past views and observations we should recognize that senescence, a retrogressive action with its meaning of growing old, also has as its antonym, juvenescence, the revitalization of lost attributes. It is ultimately the purpose of all of our studies not only to prevent the declining functions of senescence but to reclaim the vigor associated with youth. The basic elements of this discussion may be outlined.

THE EFFECTS OF 2560 r OF X-RAYS ON SPERMATOGENESIS IN THE MOUSE

1. Changes in the cellular composition of the seminiferous tubules induced by exposure to 2560 r of x-rays have been analyzed by a quantitative histological procedure. These data have been compared with the results obtained following exposure to a much lower dose (320 r) in an attempt to gain further insight with respect to the manner in which the observed changes are brought about.2. Ėxposure to 320 r results in a temporary maturation depletion of the seminiferous epithelium. This is brought about mainly by the inhibition of spermatogonial mitosis with irradiation-induced spermatogonial necrosis playing only a minor role. In contrast, exposure to 2560 r produces a permanent depletion due to the fact that surviving spermatogonia are incapable of sustained regenerative efforts.3. The frequency of necrotic spermatogonia, following 2560 r, was found to be double the peak value attained in the 320 r material, or four times that of the corresponding controls.4. Taken together, the data for the 320 r and 2560 r...