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J Löhler

Publications and source records attributed to J Löhler.

At least 73 records · Page 4Linked to original sources
PubMed1986

Normal epithelial branching morphogenesis in the absence of collagen I.

Interstitial collagens are thought to mediate epithelial-mesenchymal interactions during organogenesis. We have used the collagen I-deficient mouse mutant Mov13 to directly investigate the role of this major representative of the interstitial collagens in epithelial branching morphogenesis. Since homozygous embryos die at midgestation, we have studied the development of organ rudiments from Mov13 homozygous (i.e., collagen I-deficient), heterozygous, and wild-type embryos in culture. Development of all explants, including lung, kidney, salivary glands, pancreas, and skin, was normal by light and electron microscopic criteria and was independent of the genotype of the donor embryo. Metabolic labeling and immune staining verified the complete absence of collagen I in homozygous explants while revealing substantial production of collagens III and V in explants of all three genotypes. These results indicate either that collagen I has no role in the morphogenesis of these organs, or that its function is shared, or can be substituted for, by other fibrillar collagens.

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PubMed1985

Mechanism of recovery from acute virus infection. I. Role of T lymphocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice.

Adult mice were infected by i.v. inoculation with 10(3) mouse infectious doses of lymphocytic choriomeningitis virus (LCM virus). Despite widespread replication of the agent, overt illness did not develop; histopathologic alterations were moderate. High virus concentrations were attained in the spleen, which was chosen for further study. Cytotoxic spleen T cell responses were found to vary among inbred mouse strains, and as a rule, these were correlated with other virus-specific cell-mediated immune phenomena. However, high- and low-responder mice eliminated the virus equally fast and already at times when spleen cytotoxic T lymphocytes were just beginning to appear (and before delayed-type hypersensitivity could be demonstrated). Adoptive transfer experiments showed that very few immune T lymphocytes were capable of reducing virus replication in the recipients' spleens and, furthermore, that protection was rapidly induced; when low numbers of cells were transferred, the effect was apparent 8 hr later, and with higher numbers diminished virus replication was evident after an interval as short as 6 hr. In fact, the data suggest that virus was actually inactivated. In spite of this marked efficiency, morphologic alterations in spleens of adoptively immunized mice were absent. Attempts to reveal expansion of immune cells in the recipients have failed, and the observation that adoptive transfer was as efficient in nude mice as in their furred counterparts makes it unlikely that the recipients' T lymphocytes participated to any extent. The low number of T lymphocytes causing reduction of virus, the short interval after which the effect became measurable, and the lack of histopathologic alterations has led to a working hypothesis in which it is assumed that immunologically activated T lymphocytes secrete lymphokines that directly interfere with virus replication in neighboring cells.

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PubMed1984

Embryonic lethal mutation in mouse collagen I gene causes rupture of blood vessels and is associated with erythropoietic and mesenchymal cell death.

The role of collagen I for midgestation development was studied in homozygous Mov 13 embryos, which cannot synthesize alpha 1(1) mRNA as a result of insertional mutagenesis and most of which die between day 12 and 14 of gestation. No type I collagen was detected in mutant embryos, while the distribution of other collagens, laminin, and fibronectin was not affected. Mutant embryos develop normally up to day 12 of gestation, suggesting that collagen I has no essential role in the early phase of morphogenesis. The first pathological events were detected in hemopoietic cells of the liver, followed by necroses of mesenchymal cells in other parts of the embryo. The sudden death is caused by the rupture of a major blood vessel, indicating an important role for collagen I in establishing the mechanical stability of the circulatory system. Our results furthermore suggest that complex cell interactions in embryonic development such as those in early hemopoiesis may depend on the presence of collagen type I.

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PubMed1983

Evidence for cytotoxic T-lymphocyte-target cell interaction in brains of mice infected intracerebrally with lymphocytic choriomeningitis virus.

Murine lymphocytic choriomeningitis is a T-cell-mediated pathologic immune phenomenon. The name of this experimental illness was derived from the principal histopathologic alterations of the central nervous system (CNS) of adult mice infected intracerebrally with lymphocytic choriomeningitis virus, i.e., lymphocytic infiltrations of plexus choroidei and meninges. The general assumption that the main event in the pathogenesis is damage to virus-infected target cells by cytotoxic T-lymphocytes is plausible but direct evidence is scarce. We have studied the ultrastructural alterations of both types of cells that are thought to participate in this immunopathologic interaction. Lymphocytes with signs of T-cell transformation were first evident on day 4 after infection. One day later, lymphoblasts, often extending uropods and containing cytoplasmic dense and compound multivesicular bodies, predominated. They were sometimes seen in intimate contact with connective tissue cells of the leptomeninx and epithelial cells of the choroid plexuses which were shown to be infected by immunofluorescence procedure. Lymphoblasts occasionally invaginated the cytoplasm of the putative target cells with cytoplasmic processes, and were even found inside the latter, exhibiting the phenomenon of emperipolesis. Lymphocytic transformation was at its maximum 6 days after infection. At this time, individual leptomeningeal cells and groups of plexus epithelial cells showed signs of cytolysis, and in a few instances these damaged cells were in close spatial association with lymphoblasts. Similar observations have been reported by others who studied the interaction between cytotoxic T-lymphocytes and their appropriate targeted cells in vitro. We interpret our findings as providing direct evidence for the assumption that one link in the chain of events leading to the cerebral form of lymphocytic choriomeningitis of the mouse is damage to virus-infected leptomeningeal and plexus cells by cytotoxic T-lymphocytes.

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PubMed1983

Germline integration of moloney murine leukemia virus at the Mov13 locus leads to recessive lethal mutation and early embryonic death.

Thirteen mouse substrains genetically transmitting the exogenous Moloney murine leukemia virus (M-MuLV) at a single locus (Mov locus) have been derived previously. Experiments were performed to investigate whether homozygosity at the Mov loci would be compatible with normal development. Animals heterozygous at an Mov locus were mated, and the genotype of the offspring was analyzed. From parents heterozygous at the loci Mov1 to Mov12, respectively, homozygous offspring were obtained with the expected Mendelian frequency. In contrast, no homozygous offspring or embryos older than day 15 of gestation were obtained from parents heterozygous at the Mov13 locus. When pregnant Mov13 females at day 13 and day 14 of gestation were analyzed, approximately 25% of the embryos were degenerated. Genotyping revealed that these degenerated embryos were invariably homozygous and the normal appearing embryos were either heterozygous or negative for M-MuLV. These results suggest that integration of M-MuLV at the Mov13 locus leads to insertion mutagenesis, resulting in embryonic arrest between day 12 and day 13 of gestation. It is possible that the Mov13 locus represents a gene or gene complex involved in the early embryonic development of the mouse.

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PubMed1983

Age-dependent susceptibility of murine T lymphocytes to lymphocytic choriomeningitis virus.

In neonatal or congenital lymphocytic choriomeningitis (LCM) virus carrier mice, low numbers of T lymphocytes were always infected, but attempts to infect resting or stimulated T lymphocytes in previously uninfected adult mice have consistently failed. Only T cells in newborn mice were susceptible to LCM virus and their infection persisted when the animals grew older. Infectibility declined with increasing age of the mice. Initially, the majority was demonstrated among thymocytes, but later more splenic cells were infected. In contrast to neonatal carrier mice, in drug-induced carriers (in which persistent infection had been established later in life by immuno-suppression after infection) spleens and thymi contained initially no or a few infectious T lymphocytes; their numbers increased with the age of the mice but remained relatively low and erratic. We follow the hypothesis that LCM virus-specific immunological tolerance of carrier mice is due to age-dependent virus susceptibility of T lymphocytes and propose that murine T lymphocytes in general lack viral receptors for LCM virus, but that the few that carry LCM virus-specific immunological receptors bind the virus. If this occurs during an early stage of cellular development, infection results and functional inactivation is the consequence.

Age Factors↗
PubMed1982

De novo methylation and expression of retroviral genomes during mouse embryogenesis.

Retrovirus genomes introduced into mouse zygotes by microinjection of cloned DNA, or into morula stage pre-implantation mouse embryos by infection with Moloney murine leukaemia virus (M-MuLV), became de novo methylated and were blocked in expression. No restriction of virus expression and no de novo methylation were observed when post-implantation mouse embryos were infected with virus. Efficient de novo methylation activity may be an important characteristic of gene regulation in early mouse embryos.

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PubMed1981

Immunohistochemical demonstration of viral antigens in paraffin embedded autopsy specimens of virally infected central nervous system.

Viral antigens are preserved in routinely processed and paraffin embedded CNS tissue to an extent that they can be traced by the highly sensitive and specific unlabeled antibody method. Using this method, it was possible to visualize antigens of measles, influenza A, polio, varicella-zoster, herpes simplex, cytomegalo, parainfluenza I, lymphocytic choriomeningitis, Moloney, and Friend virus.

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PubMed1981

Ependyma and meninges of the spinal cord of the mouse. A light-and electron-microscopic study.

In addition to ependymal epithelial cells, numerous tanycytes are found along the entire central canal of the mouse. These tanycytes are arranged in clusters in the cervical, thoracic and lumbar segments of the spinal cord. In the conus medullaris, tanycytes separate and ensheath bundles of myelinated and unmyelinated axons; their processes take part in the formation of the stratum marginale gliae. In the caudal part of the spinal cord, the ventral wall of the central canal is thin and some areas are reduced to a single-cell thickness. In this region, ependymal cells participate directly in the formation of the stratum marginale gliae. The meninges consist of the intima piae, the pia mater, the arachnoid, a subdural neurothelium and the dura mater. The subarachnoid space appears occluded and opens only around the spinal roots. In the vicinity of the spinal ganglia, the dura mater, the subdural neurothelium and the arachnoid form a cellular reticulum.

Animals↗
PubMed1981

Chromosomal position and activation of retroviral genomes inserted into the germ line of mice.

The exogenous Moloney leukemia virus (M-MuLV) was inserted into the germ line of mice by exposing embryos to virus at different stages of embryogenesis. Mice derived from exposed embryos were mosaics with respect to integrated virus. Nine new substrains, designated Mov-5 to Mov-13, were derived, each of which carries a single M-MuLV genome at a different chromosomal position in its germ line. Four substrains, Mov-1 to Mov-4, were derived previously. Restriction enzyme analyses demonstrated that, with the exception of Mov-4 and Mov-6 mice, no major rearrangements or deletions have occurred in the integrated proviral genomes. Infectious virus is not activated in the majority of substrains (Mov-4 to Mov-8 and Mov-10 to Mov-12), whereas the other mice develop viremia. A detailed comparison between Mov-1 and Mov-13 mice demonstrated that the time of virus activation is different. Mov-13 mice activate infectious virus during embryogenesis, leading to a distinct pattern of virus expression in all tissues of the adult, but the viral genome in Mov-1 mice is activated only during the first two weeks after birth, leading to virus expression predominantly in lymphatic organs. Together with previous observations, at least four different phenotypes of virus expression-that is, early virus activation during embryogenesis, virus activation after birth, virus activation late in life and no expression of infectious virus at all-can be distinguished among the 13 substrains. Our results suggest that the chromosomal region at which a viral genome is integrated influences its expression during development and differentiation.

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PubMed1981

Immunopathologic alterations of lymphatic tissues of mice infected with lymphocytic choriomeningitis virus. I. Histopathologic findings.

Intraperitoneal infection with strain WE lymphocytic choriomeningitis virus led to illness in all and death in a large proportion of colony-bred NMRI mice. In their lymphoid organs, three distinct types of alterations could be distinguished: destruction of lymphocytes and mononuclear phagocytes, proliferation of lymphocytes, and fibrinoid necrosis of reticular cells and macrophages. After the intraperitoneal inoculation of 10(4) mouse infectious units, in the spleen, infectivity rapidly climbed to a peak on day 3. Virus-specific antigen, as revealed by immunofluorescence method, was first seen 2 to 3 days after infection in spleen and lymph nodes. Macrophages, reticular cells, endothelial cells, and elements of the connective tissues were positive; however, resting lymphocytes did not contain viral antigen. In both organs, immunofluorescence was maximal on day 5 and rapidly diminished thereafter. In the thymus, the concentration of infectious virus rose more slowly and virus-specific antigen, predominantly in cells resembling macrophages but never in lymphocytes, appeared later. In spleen and lymph nodes, first signs of lymphocytolysis were observed on day 3 after infection. Initially, T cells were more affected than B cells, but beginning with day 4 and thereafter, the opposite was true. In parallel with cytolysis, other lymphoid cells began proliferating. On days 4 to 5 after infection, macrophages were found to be activated. At the same time, small foci of fibrinoid necrosis made their appearance. Both lymphocytolysis and lymphoblastoid proliferation were maximal 4 to 5 days after infection, whereas fibrinoid necrosis progressed until day 6. In the thymus, first changes consisting of activation of cortical macrophages were observed on day 6, and these were followed by massive necroses of cortical thymocytes leading to extensive involution of this organ. In surviving animals, regeneration of lymphoid organs commenced around the 9th day.

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