Multiple lipomas in a bonnet monkey (Macaca radiata).
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Animals↗
Biomedical subjects
S S Majumdar
Publications and source records attributed to S S Majumdar.
Granulosa theca cell tumor with luteoma in the ovary of a bonnet monkey (Macaca radiata).
A mass was identified on the left caudal region of the abdomen in a 13-year-old bonnet monkey (Macaca radiata). The mass was excised and diagnosed as granulosa theca cell tumor accompanied with luteoma based on the microscopic findings. Morphologically it appeared pink, round, firm multilobulated measured approximately 5 x 3 x 2.5 cm in dimension. Histologically the luteoma composed of polyhedral cells with pale strained vacuolated cytoplasm, centrally located nuclei with distinct cytoplasmic borders. Granulosa theca cell tumor appeared as densely packed spindle shaped fusiform cells arranged in interlacing bundles and whorled pattern with neoplastic cells appearing irregular shaped solid sheets. The concomitant development of granulosa theca cell tumor with luteoma in a single ovary is very rare and is the first reported case in a bonnet macaque to our knowledge.
Animals↗
Sebaceous gland adenoma in a rhesus monkey (Macaca mulatta).
A tumor mass was identified below the shoulder region of a 5-year-old male rhesus monkey (Macaca mulatta). The mass was excised and diagnosed as sebaceous gland adenoma based on the microscopic findings. Morphologically it appeared as an elevated, dome-shaped, circumscribed mass of 3.6 x 2.8 x 3.2 cm in dimension with tan speckled color. Histologically, the tumor was composed of mature, sebaceous cells (sebocytes), basal cells arranged in a mass of irregular shapes and sizes, with a characteristic appearance of poly or multilobular structure. Sebocytes were well differentiated with foamy cytoplasm in the center of the lobules and poorly or undifferentiated densely staining basal cells in the periphery of the lobules. Cellular changes in the adjacent lymph node included hyperplasia of plasma cells, macrophages and lymphoid elements with typical mitosis.
Adenoma↗
Sustained activation of mitogen-activated protein kinases and activator protein 1 by the hepatitis B virus X protein in mouse hepatocytes in vivo.
Transcriptional activation of diverse cellular genes by the X protein (HBx) of hepatitis B virus (HBV) has been suggested as one of the mechanisms for HBV-associated hepatocellular carcinoma. However, such functions of HBx have been studied using transformed cells in culture and have not been examined in the normal adult hepatocytes, a natural host of HBV. Using an efficient hepatocyte-specific virus-based gene delivery system developed in our laboratory earlier, we studied the HBx action in vivo. We demonstrate that following virosome-mediated delivery of HBx DNA, a large population (>50%) of hepatocytes express the HBx protein in a dose-dependent manner, which induces a significant increase in the activity of extracellular signal-regulated kinases (ERKs) in the livers of HBx-transfected mice. Inhibition of HBx-induced ERK activation following intravenous administration of PD98059, a mitogen-activated protein kinase kinase kinase (MEK) inhibitor, confirmed the requirement for MEK in the activation of ERKs by HBx. Induction of ERK activity by HBx was sustained for up to 30 days. Interestingly, sustained activation of c-Jun N-terminal kinases (JNKs) for up to 30 days was also noted. Such constitutive ERK and JNK activation as a consequence of continued HBx expression also led to sustained stimulation of further downstream events, such as increased levels of c-Jun and c-Fos proteins along with the persistent induction of activator protein 1 binding activity. Taken together, our data suggest a critical role of these molecules in HBx-mediated cell transformation.
Animals↗
Procedures for the isolation and culture of Sertoli cells from the testes of infant, juvenile, and adult rhesus monkeys (Macaca mulatta).
The purpose of the present study was to establish culture conditions for the in vitro study of the rhesus monkey Sertoli cell (Sc) at three major stages of development, namely infancy, adulthood, and the intervening prepubertal period. Conditions for the culture of Sc from juveniles were first established using collagenase and pancreatin digestion of seminiferous tubules. The addition of 1% fetal bovine serum for the first 24 h of culture was necessary for attachment of Sc clusters. Confluency of Sc from juveniles was reached as early as 4 days of culture. Histochemical and ultrastructural observations confirmed that the cultures were enriched with Sc and that contamination by peritubular cells was minimal (2%). Although application of similar culture conditions was successful in establishing cultures of Sc from infants, significant modification of the procedure was required before Sc from adults could be cultured. Specifically, adult testicular tissue required two sequential collagenase digestions at elevated temperature. The yield of adult Sc, however, remained low. Cultures of juvenile Sc produced substantial quantities of 31-kDa inhibin, which was bioactive as reflected by its ability to suppress FSH secretion from rat pituitary cells in vitro. Although aromatase activity in juvenile Sc cultures was stimulated by FSH, inhibin synthesis, as reflected by immunoactive inhibin production and steady-state levels of alpha inhibin mRNA, was not increased by FSH. The establishment of conditions for the culture of infant, juvenile, and adult Sc from the rhesus monkey will provide a model for study of the postnatal ontogeny of Sc function in higher primates.
8-Bromo Cyclic Adenosine Monophosphate↗
Preliminary studies with recombinant chorionic gonadotropin beta-subunit produced in Escherichia coli for use as an antigen in a birth control vaccine.
PROBLEM: Prototype human chorionic gonadotropin (hCG) vaccines based on natural sources are unsuitable for widespread applications due to their complex manufacturing procedures, cost, and carrier-mediated immune suppression. METHOD OF STUDY: Wistar rats were immunized with alum-adsorbed CG beta (recombinant), CG beta-TT, and nCG beta (native CG beta)-TT, whereas Bonnet monkeys were immunized with only CG beta. The anti-hCG antibody titre in the sera obtained at different time points were quantified by radioimmunoassay. The sera of Wistar rats were characterized in terms of their affinity to hCG, bioneutralization capacity (by inhibition of hCG-induced testosterone production in Leydig cells), and cross-reactivity with human luteinizing hormone, human follicle-stimulating hormone, and human thyroid-stimulating hormone (by direct binding assays). RESULTS: Antigen-binding capacities of sera obtained upon immunization with CG beta were 3,080 +/- 943 ng/ml (n = 6) and 3,993 +/- 1,292 ng/ml (n = 4), respectively, in rats and monkeys. The analysis of data revealed that immunization of rats with CG beta produced antibodies comparable to that of CG beta-TT and nCG beta-TT. CONCLUSION: The study opens up the possibility of producing pure and highly immunogenic CG beta by a recombinant DNA route, as a consistent source of antigen for birth control vaccine.
Animals↗
Helix-loop-helix motif in GnRH associated peptide is critical for negative regulation of prolactin secretion.
The GnRH associated prolactin inhibiting factor (GAP) reveals the signature sequence associated with the helix-loop-helix structural motif. A number of different peptide fragments of GAP were designed, synthesized and analysed by circular dichroism and by an in vivo assay for prolactin secretion inhibiting activity. Peptides corresponding to the two individual alpha-helices and a 44-residue peptide comprising the entire helix-loop-helix motif show significant helical propensity in circular dichroism spectra. However, a peptide corresponding to the loop sequence shows no helical propensity. Albeit, the peptide corresponding to helix-loop-helix motif was found to inhibit prolactin secretion and augment circulating levels of gonadotropins in the in vivo assay; other shorter peptides did not show such activity. The activity profile of the 44-residue peptide was biphasic and very similar to that of the recombinant GAP. Thus, the prolactin inhibiting activity of this factor is defined by its helix-loop-helix motif as in the case of the transcription factors of developmental genes. The structural features of a homology-based model of GAP in complex with E47, a ubiquitous HLH-type developmental gene regulator, are consistent with the structural requirements of the negative regulation of transcription by helix-loop-helix proteins.
Amino Acid Sequence↗
Ligand-induced receptor dimerization may be critical for signal transduction by choriogonadotropin.
A mechanism of signal transduction by human choriogonadotropin (hCG) has been proposed. Competitive inhibition of the binding of hCG to its receptor by the serine protease inhibitors led to the identification of local structural homology of an extracellular region of the receptor with the reactive site loop of chymotrypsin inhibitor. Synthetic peptides from the extracellular domain of luteinizing hormone-choriogonadotropin (LH/CG) receptor, rationally designed on the basis of this homology, were found to affect hormone-receptor binding and bioactivity. A receptor peptide incorporating one complete structural unit of the leucine-rich repeats motif of the extracellular domain of the receptor significantly increased hCG-receptor binding in a dose-dependent manner. However, the testosterone production in a Leydig cell bioassay was inhibited in the presence of this peptide. The agonistic effect on the hCG-receptor binding and the antagonistic effect on the testosterone production of a receptor peptide suggests the possibility of more than one quasi-equivalent receptor-binding site on the hormone. Hormone-induced receptor oligomerization may therefore be involved in the mechanism of signal transduction by hCG.
Amino Acid Sequence↗
Biphasic testosterone delivery profile observed with two different transdermal formulations.
PURPOSE: Our long-term goal is to develop formulations for pulsatile testosterone (T) delivery. T has been reported earlier to show biphasic pharmacokinetics in humans by Mazer et al, as well as biphasic permeation across excised rat skin by our group. We examined two kinds of formulations to evaluate their delivery profiles and to assess whether differences in the formulation approach affect pharmacokinetics in animal models. METHODS: One formulation consisted of T and a polymer blend dissolved in isopropanol; administered by dispensing the solution on the skin to cast a film in situ. The other was an adhesive-dispersion patch. In vitro release from the patch was evaluated using a flow-through cell interfaced with an HPLC pump and UV detector. Single dose pharmacokinetics were evaluated in castrated Wistar rats and bonnet monkeys immunized against gonadotropin-releasing hormone to deplete endogenous T. RESULTS: Two maximas were observed in the T release profile from the patch and in serum concentration versus time profiles in both animal models on application of either formulation. The relative magnitudes of the two maximas and the time interval separating them were different in the case of each formulation. CONCLUSIONS: Both formulations result in biphasic pharmacokinetics of T in the animal models studied. Discrete maximas presumably correlate with "burst" and "sustained" phases of drug release.
Animals↗
A study of the relative roles of follicle-stimulating hormone and luteinizing hormone in the regulation of testicular inhibin secretion in the rhesus monkey (Macaca mulatta).
The purpose of this study was to examine the relative roles of FSH and LH in stimulating testicular inhibin secretion in the male rhesus monkey. Recombinant human (rh) FSH and rhCG were used as the gonadotropic stimuli, and juvenile rhesus monkeys, in which the endocrine activity of the pituitary-testicular axis was being driven in an adult manner with an intermittent i.v. GnRH infusion, were studied. Immunoactive inhibin levels were measured by the Monash RIA. Initiation of an intermittent i.v. infusion of rhFSH (10 IU every 3 h) resulted, after a delay of 5-6 h, in a progressive increase in the concentrations of immunoactive inhibin, which achieved, after 48 h of stimulation, a value twice that observed during vehicle treatment. Gel filtration chromatography revealed that the FSH-induced elevation in immunoactive inhibin was the result of an increase in three distinct mol wt fractions: peak I (100 kDa), peak II (50-60 kDa), and peak III (31 kDa). Although peak III accounted for most of the inhibin immunoactivity in vehicle-treated animals, peaks I and II were most responsive to FSH stimulation. Application of recently developed enzyme-linked immunosorbent assays for inhibin B and pro-alpha-C-related peptides provided additional insights into the nature of the FSH-sensitive forms of circulating immunoactive inhibin. Most notably, the 31-kDa fraction (peak III) was comprised of inhibin B and pro-alpha-C. In contrast to FSH stimulation, an intermittent infusion of rhCG (40 IU every 3 h), which markedly elevated testicular testosterone secretion, failed to increase immunoactive inhibin concentrations. These findings indicate that various forms of immunoactive inhibin are present in the circulation of the rhesus monkey, and that in this species, FSH is the principal stimulus of the secretion of testicular inhibins, including inhibin B. Additionally, they further underline the importance of the FSH-inhibin feedback loop in governing testicular function in primates.
Animals↗
Isolation and culture of Sertoli cells from the testes of adult Siberian hamsters: analysis of proteins synthesized and secreted by Sertoli cells cultured from hamsters raised in a long or a short photoperiod.
In the present study, we describe two procedures for isolation and culture of Sertoli cells from the testes of adult Siberian hamsters. In procedure I, collagenase and pancreatin were used for differential enzymatic digestion of the tissue at 32 degrees C, and effects of several attachment factors were examined. Sertoli cells isolated from adult hamsters were not affected by addition of Na selenite, epidermal growth factor, insulin, and transferrin, with or without 5% fetal bovine serum, to Dulbecco's modified Eagle's medium + Ham's F-12. Significant increase in the yield and plating efficiency of Sertoli cells was achieved by developing a novel procedure (procedure II) for Sertoli cell isolation. In this procedure, testicular tissue was exposed to only one enzyme (collagenase I) for two consecutive digestions at 37 degrees C, and the total period of enzymatic exposure was reduced relative to that of procedure I. Another objective of this study was to compare the functions of Sertoli cells isolated from spermatogenetically active and inactive adult testes. Isolated Sertoli cells from 60 +/- 5-day-old hamsters raised in long day conditions (LD, 16L:8D) or in short day conditions (SD, 6L:18D) were stimulated with FSH and testosterone in the presence of 35S-methionine for 24 h on Day 4 of culture. The medium was concentrated, and equal amounts of radioactive proteins from LD and SD hamster Sertoli cell cultures were analyzed by two-dimensional PAGE. Compared to Sertoli cells derived from SD hamsters, Sertoli cells from LD animals produced greater amounts of two secretory proteins and a smaller amount of one.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Replacement with recombinant human inhibin immediately after orchidectomy in the hypophysiotropically clamped male rhesus monkey (Macaca mulatta) maintains follicle-stimulating hormone (FSH) secretion and FSH beta messenger ribonucleic acid levels at precastration values.
This study directly tested the inhibin hypothesis by examining the ability of replacement with recombinant human (rh-) inhibin, either alone or in combination with testosterone (T), to maintain FSH secretion and FSH beta messenger RNA (mRNA) at intact levels after orchidectomy in the hypophysiotropically clamped juvenile rhesus monkey. Thirteen male monkeys (11-21 months of age) received an intermittent i.v. infusion of GnRH (0.1 microgram/min for 3 min every 3 h). After 4-6 weeks of GnRH stimulation, 10 animals were orchidectomized, and 3 monkeys were sham castrated. Hormone replacement was initiated at castration and maintained for 4 days. Three monkeys received a combination of inhibin and T replacement, 4 monkeys received replacement with inhibin alone, and 3 monkeys received T replacement alone. A continuous i.v. infusion of rh-inhibin (832 ng/h.kg) was used to replace the testicular protein, whereas SILASTIC capsules were implanted sc for T replacement. The FSH response to castration and hormone replacement was determined by measuring circulating concentrations of this gonadotropin before a GnRH pulse and for 3 h thereafter on the day before surgery and on days 2 and 4 postcastration. Circulating immunoactive inhibin was measured by a RIA that recognizes the free alpha-subunit of inhibin as well as inhibin dimers. At the end of the study, anterior pituitaries were collected for analysis of steady state levels of FSH beta, LH beta, and alpha-subunit mRNAs. Steroid replacement alone, which produced circulating T concentrations in the upper physiological range, failed to prevent the postcastration increases in circulating FSH concentrations and pituitary FSH beta mRNA levels. In contrast, when circulating immunoactive inhibin in T-replaced monkeys was maintained at precastration levels (approximately 2 ng/ml) by infusion of rh-inhibin, FSH secretion and synthesis were held at control values. When T was omitted from combined replacement, the FSH-suppressing action of the recombinant hormone was not compromised. These results demonstrate that rh-inhibin is biologically active in the monkey, and the action of inhibin to suppress FSH synthesis and secretion does not require a concomitant action of T. Moreover, because the hypophysiotropic drive to the pituitary-testicular axis was clamped, the FSH-suppressing action of rh-inhibin must be at the pituitary.
Analysis of Variance↗
Vitamin D modulates the effects of follicle-stimulating hormone on Sertoli cell function and testicular growth in Siberian hamsters.
Sertoli cells from immature (18-20 day old) Siberian hamsters (Phodopus sungorus) raised in a long photoperiod (LD; 16hL:8hD) or a short photoperiod (SD; 6hL:18hD) were cultured and exposed to follicle-stimulating hormone (FSH) and/or vitamin D3 (D3) in vitro. D3 did not stimulate lactate production when added alone, but significantly augmented the stimulatory action of FSH on lactate production by Sertoli cells from both LD- and SD-exposed hamsters. Hamsters raised in LD or SD were injected daily with D3 for 10 days starting at 18 days of age. This treatment resulted in a significant increase in the testicular weight of hamsters raised in LD in which circulating FSH levels are high. In contrast, testicular weight was not altered by D3 treatment in SD hamsters in which circulating levels of FSH are low. We conclude that D3, probably after hydroxylation to 1,25(OH)2 vitamin D3, modulates the action of FSH on testicular growth and Sertoli cell function.
Animals↗
Assessment of the role of follicle-stimulating hormone and prolactin in the control of testicular endocrine function in adult djungarian hamsters (Phodopus sungorus) exposed to either short or long photoperiod.
Exposure of adult male Djungarian hamsters (Phodopus sungorus) to a short photoperiod induces testicular atrophy. To evaluate the role of FSH and prolactin (PRL) in the control of testicular endocrine function, adult Djungarian hamsters were exposed to either a long photoperiod (16L:8D per day) or a short photoperiod (6L:18D per day) for 11 wk. After 11 wk, hamsters housed in each of these photoperiods were placed into three groups and treated s.c. daily for 7 days with 50% polyvinylpyrrolidone in saline (SAL-PVP), rat FSH (10 micrograms/hamster/day) in SAL-PVP, or ovine PRL (100 micrograms/hamster/day) in SAL-PVP. On Day 8, animals in each of these groups received i.p. injections of saline or ovine LH (0.3 microgram/g BW); 1 h later, blood was obtained by cardiac puncture under ether anesthesia. Plasma FSH, LH, PRL, androstenedione (A-dione), and testosterone levels were measured by validated RIAs. In hamsters kept in the short photoperiod, testicular weight was decreased (p < 0.001). In these animals, FSH treatment increased (p < 0.001) testicular weight, whereas PRL injections had no effect. Testicular weight in animals kept in the long photoperiod was unaffected by FSH or PRL treatment. After 12 wk of exposure to the short photo-period, circulating PRL levels were undetectable; plasma levels of FSH (p < 0.001), LH (p < 0.05), A-dione (p < 0.005), and testosterone (p < 0.001) were significantly reduced. Administration of either FSH or PRL had no influence on plasma A-dione levels in hamsters exposed to either photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS)
Androstenedione↗
The follicle stimulating hormone-inhibin feedback loop in male primates.
This paper reviews our current knowledge of the role of testicular inhibin in the regulation of follicle stimulating hormone (FSH) secretion in the rhesus monkey. Species differences between monkey and rat are described, and evidence for and against the hypothesis that control of FSH secretion in the human male is similar to that for the monkey is presented.
Animals↗
Cholecystokinin stimulates gonadotropin-releasing hormone release in the monkey (Macaca mulatta).
There is evidence to suggest that the arginine vasopressin release observed in association with emesis after i.v. injection of cholecystokinin (CCK) and N-methyl-D-aspartate (NMDA) is mediated by stimulation of emetic centers in the brainstem. That the GnRH-releasing action of NMDA is also sometimes accompanied by emesis led to the suggestion that stimulation of this parvocellular system by the glutamate agonist may also be mediated in part via activation of brainstem pathways. If this is the case, then other nauseogenic agents, such as CCK, should similarly elicit GnRH release. The foregoing prediction was tested in the castrated juvenile male monkey, an experimental model characterized by the absence of spontaneous GnRH release. GnRH discharges were monitored indirectly by measuring changes in circulating LH concentrations after the responsivity of the gonadotroph had been heightened by a chronic intermittent i.v. infusion of the decapeptide. An i.v. bolus of CCK at 10 and 30 micrograms/kg BW led to a distinct discharge of GnRH accompanied by emesis or other behaviors suggestive of nausea. Lower doses of CCK (1 and 3 micrograms/kg BW) failed to significantly perturb GnRH release or cause emesis, although NMDA (5 mg/kg BW; racemic form) injected i.v. 3 h after the CCK challenge led to a robust rise in GnRH. In a parallel study, three repetitive i.v. CCK injections at 2h intervals maintained intermittent GnRH release. Pretreatment with a long-acting GnRH receptor antagonist ([AcD2Nal1,4ClPhe2,DTrp3,DArg6,DAla10]GnRH -HOAc) abolished the LH response to CCK, confirming that the action of this peptide was mediated by GnRH release. Although a direct hypothalamic site of action for these agents remains the most likely possibility, since both NMDA and CCK receptors are present in the infundibular region, the present data are consistent with the notion that CCK and, by inference, NMDA may activate GnRH release in part via the stimulation of brainstem emetic centers. Plasma GH, PRL, and cortisol concentrations were also monitored during the course of some of these experiments, and the release of these hormones was observed after the administration of either the 10 or 30 micrograms/kg BW dose of CCK.
Animals↗
Differential response of testis and serum gonadotropins to testosterone in rats treated with a gonadotropin releasing hormone antagonist or estradiol 17 beta.
Adult rats treated with a GnRH antagonist (Ac D2Nal1, D4Cl Phe2, DTrp3, DArg6, DAla10 GnRH; code: 103-289-10, National Institutes of Health, USA) for 5 weeks (250 micrograms/kg b.w) showed multiple degrees of impairment and atrophy of the genital organs concomitant with decreased serum levels of testosterone, LH and FSH. Inhibition of spermatogenesis was characterized by germ cell degeneration and overall decline in different cell numbers and in particular, spermatids of any kind were completely absent. Testosterone supplementation (60 micrograms/rat/day, sc) to GnRH antagonist treated rats, for the same period, significantly elevated the weights of the sex organs, and the serum levels of hormones. Spermatogenesis was improved both qualitatively and quantitatively; albeit failed to be restored back to control levels. Treatment with estradiol 17 beta (1 microgram/rat/day) for 5 weeks had insignificant effect on spermatogenesis but the weights of the genital organs (seminal vesicles by 19% and ventral prostate by 40%) and the levels of serum hormones (LH by 24%, FSH 22% and testosterone by 25%) were otherwise reduced. Administration of testosterone either alone or in combination with estradiol 17 beta had only a marginal effect on spermatogenesis or on other reproductive parameters. The results indicate a positive shift in the response of the testis and serum levels of gonadotropins to testosterone supplementation in rats treated with either GnRH antagonist or estradiol 17 beta.
Animals↗
Fertility of transgenic female mice expressing bovine growth hormone or human growth hormone variant genes.
Although growth hormone (GH) exerts various direct and indirect stimulatory effects on gonadal development and function, excessive levels of GH in acromegalic patients and in transgenic animals are often associated with reproductive disorders. We have examined reproductive performance of transgenic female mice expressing the following hybrid genes: mouse metallothionein-1 (MT)/human placental GH variant (hGH.V), MT/bovine GH(bGH), and phosphoenolpyruvate carboxykinase (PEPCK)/bGH. This allowed us to evaluate the effects of chronic GH excess in three animal models and to obtain some information on the significance of the lactogenic activity of the foreign GH (hGH.V vs. bGH) and on the developmental stage of transgene expression (MT vs. PEPCK). Transgenic animals from each line had elevated plasma insulin-like growth factor-I levels and greatly increased adult body weight. Plasma bGH levels were significantly higher in PEPCK/bGH than in MT/bGH transgenic mice. Approximately 20% of transgenic MT/hGH.V and MT/bGH females and over 60% of transgenic PEPCK/bGH females were infertile. Transgenic females that did reproduce ovulated either a normal or increased number of eggs but exhibited a variety of reproductive disorders including increased interval between pairing with a male and conception, increased interval between litters, reduced number of litters, reduced fetal growth, increased pre- and postnatal mortality, and alterations in sex ratio. Among adult offspring of these females, the proportion of transgenic animals was significantly less than the expected 50%. While some characteristics (e.g., fetal crown-rump length and weight on Day 14 of pregnancy) were affected to a comparable extent in transgenic females from all three lines, MT/hGH.V and PEPCK/bGH females were, in general, more severely affected than the MT/bGH animals. Sterility of PEPCK/bGH females appeared to be due to luteal failure since treatment with progesterone led to pregnancy. Greatly increased intervals between successive litters appeared to be due to failure to mate during postpartum estrus and to sterile matings during this period. Reduced fetal size and weight may have been due to chronic glucocorticoid excess because comparable changes could be induced in normal females by injections of dexamethasone during pregnancy, and plasma corticosterone levels were previously shown to be elevated in transgenic mice from each of these lines. Comparison of these results with data obtained from matings of normal female mice to transgenic males from the same lines suggests that reduced fetal growth is due primarily to maternal genotype, while reduced "transmission" of the hybrid genes is not, and presumably reflects increased mortality of transgenic progeny at various stages of development.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗