Female Founders Research Articles

An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis.

Transgenic mice expressing high levels of the BclxL or Bcl2 proteins in the male germinal cells show a highly abnormal adult spermatogenesis accompanied by sterility. This appears to result from the prevention of an early and massive wave of apoptosis in the testis, which occurs among germinal cells during the first round of spermatogenesis. In contrast, sporadic apoptosis among spermatogonia, which occurs in normal adult testis, is not prevented in adult transgenic mice. The physiological early apoptotic wave in the testis is coincident, in timing and localization, with a temporary high expression of the apoptosis-promoting protein Bax, which disappears at sexual maturity. The critical role played by the intracellular balance, probably hormonally controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in normal mouse testis) in this early apoptotic wave is shown by the occurrence of a comparable testicular syndrome in mice defective in the bax gene. The apoptotic wave appears necessary for normal mature spermatogenesis to develop, probably because it maintains a critical cell number ratio between some germinal cell stages and Sertoli cells, whose normal functions and differentiation involve an elaborate network of communication.

Specific arrest of spermatogenesis caused by apoptotic cell death in transgenic mice.

The c-myc protooncogene has been implicated in the control of cell proliferation, differentiation and/or apoptosis in various cellular systems. However, the role of c-myc in germ cell lineage is largely unknown. We have produced transgenic mouse lines carrying the rat c-myc protooncogene under the control of human metallothionein promoter (hMT-c-myc). It was found that the male transgenic mice were sterile. In contrast, all of the female transgenic mice were completely fertile and transmitted the transgene to the next generation. However, male transgenic mice from the female transgenic founders were also found to be sterile. This sterility was due to a defect in spermatogenic cell differentiation, since virtually no sperm were seen within the seminiferous tubules or the cauda epididymis. Histological examination revealed that germ cell death occurred approximately 7 days after birth and, consequently, spermatogenesis was arrested at an early stage in meiotic division in the transgenic mice. Moreover, this germ cell death was found to be caused by apoptosis. We conclude that an excess level of c-myc expression in differentiating spermatogenic cells is responsible for the apoptotic death of germ cell, and that a decrease in c-myc level would be an obligatory step for the completion of normal spermatogenesis.

Corner's caring contribution

The BBC has obviously realised that the market for programmes about sexy young modern doctors is completely saturated. We've got Casualty, ER, Chicago Hope, Northern Exposure, Country Practice, GOS, Jimmy's—need I go on? Hence the Pioneers series, looking at medical innovators of the 20th century, which continued on BBC2 on Monday with “Beryl's Babies.” This was a programme about the female founder of the Bristol's first special care baby unit, Dr Beryl Corner. She made an astounding contribution to modern neonatal care with her work on retinopathy of prematurity and kernicterus and achieved all this in an …

The Genetics of Retinoblastoma, Revisited

The fact that all individuals are not identical in their risk for certain cancers has been known for many years. The factors responsible for the increased risk observed in certain individuals, families, or populations may be either environmental or genetic. The genetic risk factors identified to date generally result in a greatly increased relative risk – on the order of ten to one hundred thousand-fold in the case of familial retinoblastoma, for example. The major reason for the identification of genetic factors that result in such large increases in relative risk is that the transmission of such genes in families results in an easily identifiable pattern of inheritance and the concommitant ability to locate the gene resulting in increased risk by genetic linkage analysis. From our study of sporadic and familial retinoblastoma, we have identified a genetic factor whose action appears to result in a more modest increase in relative risk – on the order of one-hundred to one-thousand-fold. We believe that a locus that is responsible for this increase in relative risk lies on the human X-chromosome. Our data indicate that aberrant alleles at this locus not only appear to increase an individual's risk for a number of cancers, but also participate in the process of genome imprinting.The epidemiological and genetic arguments in favor of the involvement of an X-linked “imprintor, mutator” gene in the generation of new, heritable, RB-1 mutations are given in detail in Naumova and Sapienza (1994). The pertinent data may be summarized as follows:1. there is a significant excess-of-males among patients with bilateral sporadic but not unilateral sporadic retinoblastoma;2. there is preferential retention of paternally-derived RB-1 alleles in bilateral, but not unilateral, sporadic retinoblastoma;3. sex ratio bias in favor of males is observed among the offspring of male founders but not female founders of retinoblastoma pedigrees (i.e. the male founders fail to transmit their X-chromosomes with the expected frequency;4. transmission ratio distortion in favor of affected individuals is observed among the offspring of male founders but not female founders, and5. the affected male offspring of these male founders have families in which offspring are distributed equally among affected and unaffected boys and girls, as expected for an autosomal dominant trait, i.e. sex-ratio and transmission-ratio distortion are observed only among the offspring of male founders of retinoblastoma pedigrees.

Boar proacrosin expressed in spermatids of transgenic mice does not reach the acrosome and disrupts spermatogenesis.

Transgenic mice that express boar proacrosin were produced to examine mechanisms for targeting hydrolytic enzymes to the acrosome. A 2.3 kb transgene was constructed by ligating the cDNA for boar preproacrosin with the mouse protamine 2 promoter region. Six founder mice that incorporated the transgene were identified by polymerase chain reaction and Southern blot analysis. Northern blots indicated that the two male founders (Ac.2 and Ac.5) and male progeny from three female founders (Ac.3, Ac.4, Ac.6) expressed the transgene mRNA in testis, but not in somatic tissues. In these transgenic animals boar proacrosin was detected by immunohistochemistry in condensing spermatids, but was not localized in the acrosome. This acrosomal targeting defect of the transgene product may result from its delayed expression during the later steps of haploid differentiation. Furthermore, both male founders and all Ac.4 and Ac.6 males were infertile, as determined by multiple matings for at least 2 months. Ac.3 males were either infertile or rarely transmitted the transgene to their offspring. The infertile males mated, produced copulatory plugs, and had seminal vesicle weights and testosterone levels within the normal range. However, they produced significantly fewer spermatozoa and had lower testis weights than controls. Although the mitotic and meiotic phases of spermatogenesis appeared normal by histological criteria, condensing spermatids were missing from most tubules, and multinucleated cells were present in the lumen of seminiferous tubules and in the epididymis. We hypothesize that boar proacrosin which fails to reach the acrosome is activated in these transgenic mice, and that its proteolytic activity disrupts spermatogenesis during spermatid formation.

Social Reconstruction through Education: The Philosophy, History, and Curricula of a Radical Ideal

Is Social Transformation Always Progressive? Rightist Reconstructions of Schooling Today, Michael W. Apple The Social Frontier 1934-1943: Retrospect and Prospect, James R. Giarelli Red Teachers Can't Save Us: Radical Educators and Liberal Journalists in the 1930s, James Wallace Harold Rugg's Social Reconstructionism, Peter F. Carbone and Virginia S. Wilson Female Founders and the Progressive Paradox, Susan F. Semel Southern Progressivism During the Great Depression: Virginia and Black Social Reconstruction, Michael James Social Recon-structionism for 21st Century Educators, William O. Stanley and Kenneth D. Benne

Passionate Enlightenment: Women in Tantric Buddhism

The crowning cultural achievement of medieval India, Tantric Buddhism is known in the West primarily for the sexual practices of its adherents, who strive to transform erotic passion into spiritual ecstasy. Historians of religion have long held that the enlightenment thus attempted was for men only, and that women in the movement were at best marginal and subordinate and at worst degraded and exploited. Miranda Shaw argues to the contrary, presenting extensive new evidence of the outspoken and independent female founders of the Tantric movement and their creative role in shaping its distinctive vision of gender relations and sacred sexuality. Drawing on interviews and archival research conducted during two years of fieldwork in India and Nepal, including more than 40 works by women of the Pala period, the author reinterprets the history of Tantric Buddhism during its first four centuries. In her view, the Tantric theory of this period promotes an ideal of co-operative, mutually liberative relationships between women and men while encouraging a sense of reliance on women as a source of spiritual insight and power.

Overexpression of TGF-beta 1 in the central nervous system of transgenic mice results in hydrocephalus.

Transforming growth factor beta (TGF-beta) has been proposed to play a number of roles in central nervous system (CNS) development and response to injury. To test these proposals, transgenic mice were generated which overproduce TGF-beta 1 in the CNS. Surprisingly, these mice developed severe hydrocephalus and died between birth and 3 weeks of age. Ovary transplantation from an affected female founder has permitted perpetuation of one of the lines as a hydrocephalus model whose genetic defect is known. These results also demonstrate that the developing CNS is highly sensitive to TGF-beta, and suggest a role for aberrant expression of TGF-beta in the pathogenesis of developmental disease of the CNS.

Aberrant reproductive phenotypes evident in transgenic mice expressing the wild-type mouse estrogen receptor.

The estrogen receptor (ER) acts as a transcription factor to regulate multiple cellular functions involved in normal physiology, differentiation, and reproduction. To date, there is no known animal model for studying aberrant ER expression. Therefore, we created transgenic mice expressing the wild-type mouse ER under the control of the mouse metallothionein-I (MT) promoter to determine whether overexpression of the ER would disrupt normal reproductive processes. Five male and one female founder mice were produced, and all were fertile. The progeny from these mice were screened for MT-mER expression by the ribonuclease protection assay. Mice in all six lines were found to express the transgene in a variety of tissues, although generally at low levels. The highest level of expression was observed in the female reproductive tract of line E. Females in all six lines demonstrated aberrant reproductive phenotypes involving processes at parturition and, with some of the lines, a tendency toward reduced fertility. Gestational length was prolonged up to 4 days beyond the normal gestation of 19 days, providing evidence of delayed parturition. In addition, prolonged labor (up to 3 days in length to deliver all pups) and labors requiring cesarean sections for maternal survival demonstrated the occurrence of dystocia in the MT-mER females. As maternal age increased, the incidence of stillborn litters, delayed parturition, and dystocia approached 100% in the transgenic dams. Difficulties at parturition were not observed in nontransgenic control females. These phenotypes suggest that the mechanisms regulating parturition may be perturbed by improper expression of the ER. The MT-mER transgenic mice may provide a novel approach for studying the estrogen-regulated signals involved in parturition and fertility as well as a unique animal model for the human reproductive phenotypes of delayed parturition and dystocia.

Female Founders of STS

Female Founders of STS

Effect of maternal aging on transgene heritability in transgenic founder mice derived from zygotes microinjected with retroviral long terminal repeat-containing recombinant deoxyribonucleic acid.

To determine the stability of artificially introduced recombinant DNA in the mouse germline throughout the reproductive life, founder mice derived from fertilized eggs injected with retroviral long-terminal-repeat-containing recombinant DNAs were mated with congenic FVB/N mice. Tail DNA of all progeny were screened and restriction fragment patterns of the transgenes were examined. Litter size and percentage of transgene transmission at various reproductive age periods were analyzed. Microinjection of 1737 eggs with four different recombinant DNAs resulted in 12 female and 11 male transgenic mice; 2 males were sterile and the remaining 21 mice served as founders to produce 1087 F1 progeny. With increasing parental age, litter size decreased generally. The percentage of progeny inheriting the transgenes declined markedly with increasing aging of 4 female founders; this aging effect was not observed in male founders (p < 0.005). No apparent change in transgenes was detected in progeny from late reproductive stages.

Molecular identification of a Mandrillus hybrid using mitochondrial DNA

AbstractThe purity of the Melbourne Zoo mandrill (Mandrillus sphinx) population has been questioned, based on the facial coloration of the female members. Consequently, it is believed that the original founding female of the Melbourne Zoo “mandrill” population was a drill–mandrill hybrid. This individual, whose mother was suspected to be a drill (Mandrillus leucophaeus), is the only female to have contributed mitochondrial DNA (mtDNA) to the population. The strictly maternal inheritance of mtDNA in vertebrates makes this molecule an ideal marker for the tracing of maternal gene flow. DNA sequence data from a 307‐base pair (bp) region of the mitochondrial gene cytochrome b, amplified via the poly‐merase chain reaction (PCR), was obtained from the Melbourne Zoo individuals, and compared to the homologous sequences from known specimens of both mandrill and drill. The results obtained show that all current members of the “mandrill” population possess drill mtDNA, supporting the belief that the original female founder was a hybrid. This type of genetic study has significant implications for the conservation and future management of this and other captive populations. © 1993 Wiley‐Liss, Inc.

The allegory of female authority: Christine de Pizan's Cité des dames (review)

Reviews 233 accompany the stanzas. Norse poetic terminology is usually rendered by the 'basic' meaning so that for example, w e find 'sword' rather than 'swinging twig of the mailcoat' in the translation of 'Egill's duel with Lj6tr', stanza two. In Poole's exposition the reader is frequently, though not invariably, aided by translations of short Norse phrases and should rarely have great difficulty in following the argument. Some readers may feU that the author is occasionally over-generous in detecting unity in his texts but his case is always carefully argued and generally it is convincing. The book is attractively presented on acid-free paper, with a useful twelvepage bibliography. Slightly regrettable, as introducing an amateurish touch into an otherwise very professional production, is the representation of the letter 'eth' by a 'd' with a horizontal stroke through it. 'Thorn' was, however, available to the printer. The statement in the 'blurb' on thefirstpage that what Poole calls 'Fri ger arflokkr' is an extract from Sextefha is both surprising and unsupported elsewhere in the volume. One abbreviation used in the bibliography, ASB (for Altnordische Saga-Bibtiothek) is omitted from the 'Abbreviations'. In his acknowledgements Poole speaks of his 'attempts to survey Ultima Thule from the distant perspective of Tena Australis Incognita'. This latest addition to the small band of Norse monographs with an 'Antipodean' connection should be welcomed by all interested in skaldic poetry qua poetry or in the role that the verse plays in the fslendingasogur and konungaso'gur. John Kennedy School of Information Studies Charles Sturt University, Riverina Quilligan, Maureen, The allegory of female authority: Christine de Pizan's Cite" des dames, Ithaca and London, Cornell University Press, 1991; cloth and paper; pp. xv, 290; 41 illustrations; R.R.P. US$49.50 (cloth), $16.45 (paper). Like Stephen Hawking's A brief history of time, Christine de Pizan's Livre de la citi des dames is, one suspects, a book much talked about but litde read. Maureen Quilligan's The allegory offemale authority, which more than fulfils its intention 'to help to make the text of the Citi des dames more readable' (p. 4), should do much to conquer reader reluctance for this 15th-century prose allegory about the construction of a female bastion, designed both as a refuge from the assaults of medieval misogyny and as monument to the achievements of outstanding women. The scope and theoretical underpinning of Quilligan's eloquent study belie its modest claim to be 'essentially a page-by-page commentary' (p. 2) on the Cite. Beginning with an eloquent plea for consideration of Christine's distinctive authorial persona before m o d e m critical theory completes the 234 Reviews authorial obituary, Quilligan's thesis is that the central issue of the Cite" is female authority: literary, maternal, and poUtical. What foUows is an absorbing, multi-leveUed analysis, ranging from the Citi's central architectural metaphor to discussion of its reconstruction of male 'precursor texts' which provide the Citfs literary grist such as Boccaccio's De mulieribus Claris and Decameron and the Speculum historiale of Vincent de Beauvais, Christine's construction of its gender specific voice ('Je, Christine'), and her self-positioning vis-a-vis the audores of the medieval literary canon. To the accompaniment of narratives about famous women from the Bible, history and legend, which are delivered by three personified female figures of authority, Reason, Justice and Droitture (Rectitude), 'Christine' sets about the composition of her textual city. In Reason's opening histories of female city founders, maternality, Quilligan argues, becomes an instrument which legitimizes female martial and political power and emerges as a continuing focus of psychoanalytical interest in the Cite'. The insertion of a female martyrology, which is without parallel in Boccaccio, into the last section of the work is, she suggests, a move against the authority of that auctor and a representation of martyrdom as a 'political' process, which publicly celebrates female authority over self and earthly power. The allegory concludes with an apologia in defence of the conservative ending to the Cite", which enjoins w o m e n to be virtuous wives, widows and virgins. Christine's politics, must in Quilligan's view...

High frequency of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice created from two different strains of mice

Transgenic mice were developed by injecting a mouse metallothionein promoter-human growth hormone (Mt-hGH) gene fragment into the pronucleus of C57BlxDBA/2J-f 2 or C57BlxCBA-f 2 one cell embryos. Six founder animals with the C57BlxDBA genetic background grew 1.3–2.2 times larger than littermate controls and had higher levels of hGH in plasma (4.6–279 mU/1). Three of the four female transgenic founders developed malignant papillar adenocarcinomas of mammary origin at 27–43 weeks of age. One male transgenic founder was successfully mated and two of three female transgenic offsprings developed mammary tumors. To examine if the tumor induction was dependent on the strain of mice used the experiments were repeated using animals with different genetic background. Fourteen female hGH transgenic mice from five founder animals were generated using C57BlxCBA-f 2 mice. Thirteen of the animals had elevated levels of hGH in plasma (7–1960 mU/1) and grew larger than control animals. Nine of the animals developed mammary adenocarcinomas. Four of the hGH expressing animals did not demonstrate macroscopic tumor formation but have not yet been analyzed histologically. The present study suggests that markedly elevated endogenous levels of GH cause mammary carcinoma in hGH transgenic mice. The present animal model might prove useful for studying molecular mechanisms involved in the development of hormonally induced mammary tumors.

Over-expression of an endogenous milk protein gene in transgenic mice is associated with impaired mammary alveolar development and a milchlos phenotype

The whey acidic protein (WAP) gene is expressed in mammary epithelial cells at late pregnancy and throughout lactation. We have generated transgenic mice in which a mouse WAP transgene is expressed precociously in pregnancy. From 13 founder mice bearing WAP transgenes, two female founders and the daughters from a male founder failed to lactate and nurture their offspring. We named this phenotype milchlos. Mammary tissue from postpartum milchlos mice was underdeveloped, contained too few alveoli and resembled the glands of non-transgenic mid-pregnant mice. The hypothesis that alveolar development in milchlos mice was functionally arrested in a prelactational state is consistent with low levels of α-lactalbumin mRNA, and an unidentified keratin RNA in mammary tissue from postpartum mice. Defects in alveolar function in milchlos mice were detected at mid-pregnancy; in non-transgenic mice, WAP was secreted into the alveolar lumen but remained preferentially in the cytoplasm of the alveolar epithelial cells in the milchlos mice. Since deregulated WAP expression resulted in impaired mammary development, it is possible that WAP plays a regulatory role in the terminal differentiation and development of mammary alveolar cells.

Induction of mammary adenocarcinomas in metallothionein promoter‐human growth hormone transgenic mice

To develop transgenic mice, a mouse metallothionein promoter-human growth hormone (Mt-hGH) gene fragment was injected into the pronucleus of C57BI x DBA/2J F2 one-cell embryos. Six founder animals grew larger (1.3-2.2 times) than littermate controls and had higher levels of hGH in plasma (4.6-279 mU/l). At 27-43 weeks of age, 3 of the 4 female transgenic founders developed malignant papillary adenocarcinomas of mammary origin. One of the male transgenic founders was successfully mated and 2 of 3 female transgenic offspring developed mammary tumors. Forty-two female mice with the same genetic background as the transgenic animals and older than 43 weeks served as controls. No palpable tumor was found in this group. Five of the control animals were killed and examined histologically, revealing only normal mammary tissue. Earlier studies have shown that GH is important for growth and development of the mammary gland. Our study suggests that markedly elevated endogenous levels of GH cause mammary carcinoma in a specific strain of transgenic mice. The present animal model might be useful for studying molecular mechanisms that are involved in the development of hormonally induced mammary tumors.

Conservation Genetics of the Endangered Isle Royale Gray Wolf

Abstract. The small group of wolves on Isle Royale has been studied for over three decades as a model of the relationship between large carnivores and their prey. During the last ten years the population declined from 50 individuals to as few as 12 individuals. The causes of this decline may be food shortages, disease, or reduced genetic variability. We address the issues of genetic variability and relationships of Isle Royale wolves using allozyme electrophoresis, mtDNA restriction‐site analysis, and multilocus hypervariable minisatellite DNA analysis (genetic fingerprinting). Our results indicate that approximately 50% of the allozyme heterozygosity has been lost in the island population, a decline similar to that expected if no immigration had occurred from the mainland. The genetic fingerprinting data indicate that the seven sampled Isle Royale wolves are as similar as captive populations of siblings. Surprisingly, the Isle Royale wolves have an mDNA genotype that is very rare on the mainland, being found in only one of 144 mainland wolves ThFF suggests that the remaining Isle Royale wolves areprobably derived from a single female founder

Transcending a Patriarchal Past: Teaching the History of Women in Sociology

The lives and ideas of early female sociologists are rarely documented in textbooks, classrooms, or historical accounts of the profession. This patriarchal legacy is rejected by an increasing number of contemporary sociologists. These more egalitarian professionals soon discover, however, that they have few resources in their sociological stock of knowledge to guide them in this new enterprise. This paper is a guide for teachers in a variety of courses who want to start filling these deep gaps in knowledge. Specific guidance is provided on reference works, autobiographies, and biographies that provide information on 10 early female founders of American sociology. Given these references and our capacity to innovate and recreate our social world, we have a sufficient stock of knowledge to change our sociological practice in the classroom.

EVOLUTIONARY RELATIONSHIPS AMONG COLONIES OF COLUMBIAN GROUND SQUIRRELS AS SHOWN BY MITOCHONDRIAL DNA.

Mitochondrial DNA (mtDNA) from 71 Columbian ground squirrels (Spermophilus columbianus) collected in 12 locations in western Canada were assayed for restriction-site variation with 10 endonucleases. Five of these endonucleases revealed variant patterns, and the composite genotypes were used to develop a linear transformation series among the mtDNA genotypes. Two of the four clones had a wide distribution, while the remaining two clones were geographically restricted. The mtDNA of Columbian ground squirrels was also compared to two other species of Sciuridae: Richardson's ground squirrels (S. richardsonii) and Arctic ground squirrels (S. parryii). Calculation of divergences from fragment length and restriction-site data indicated that Arctic ground squirrels and Richardson's ground squirrels were more closely related to each other than either was to Columbian ground squirrels. The transformation series among clones within the Columbian ground squirrels was rooted using Richardson's and Arctic ground squirrels as out-groups. From these data, we conclude that the colonization by female founders of Columbian ground squirrel populations occurred after deglaciation along the eastern ranges of the Rocky Mountains, while colonies on the western ranges may have been present before extensive deglaciation occurred, having existed in refugia in northwestern Alberta.

Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice.

The activated human Ha-ras oncogene was subjected to the control of the promoter region of the murine whey acidic protein (Wap) gene, which is expressed in mammary epithelial cells in response to lactogenic hormones. The Wap-ras gene was stably introduced into the mouse germ line of five transgenic mice (one male and four females). Wap-ras expression was observed in the mammary glands of lactating females in two lines derived from female founders. The tissue-directed and hormone-dependent Wap expression was conferred on the Ha-ras oncogene. The signals governing Wap expression are located within 2.5 kilobases of 5' flanking sequence. The other two lines derived from female founders did not express the chimeric gene. In the line derived from the male founder, the Wap-ras gene is integrated into the Y chromosome. Expression was found in the salivary gland of male animals only. After a long latency, Wap-ras-expressing mice developed tumors. The tumors arose in tissues expressing Wap-ras--i.e., mammary or salivary glands. Compared to the corresponding nonmalignant tissues, Wap-ras expression was enhanced in the tumors.