RESUMO
Connexin proteins make intercellular channels - gap junctions - which provide a direct pathway for cell-cell signaling in vertebrates. Studies of mice lacking connexin genes have demonstrated the need for intercellular transfer of messenger molecules and are uncovering the specific functions of each connexin.
Assuntos
Comunicação Celular/fisiologia , Conexinas/fisiologia , Junções Comunicantes/fisiologia , Animais , Feminino , Camundongos , Camundongos Knockout , Oogênese/fisiologia , Ovulação/fisiologia , TransgenesRESUMO
Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) is an excellent model for human multiple sclerosis. Within the BALB/c strain, BALB/cAnNCr mice are susceptible while BALB/cByJ mice are resistant. BALB/cByJ mice become susceptible when irradiated. Adoptive transfer of CD8+ splenic T cells from resistant BALB/cByJ donors protect irradiated BALB/cByJ, as well as BALB/cAnNCr recipients, from development of TMEV-IDD. Anti-TMEV CTL activities in BALB/cAnNCr, BALB/cByJ and irradiated BALB/cByJ mice are comparable. A population of splenic CD4+ T cells in BALB/cByJ donors has also been identified which can protect both susceptible BALB/cAnNCr and irradiated BALB/cByJ recipients from TMEV-IDD via adoptive transfer.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Doenças Desmielinizantes/imunologia , Theilovirus/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Transplante de Células , Doenças Desmielinizantes/virologia , Suscetibilidade a Doenças , Fibrossarcoma , Raios gama , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neuroimunomodulação/imunologia , Baço/citologia , Baço/imunologia , Baço/efeitos da radiação , Timectomia , Células Tumorais CultivadasRESUMO
SWR/J mice are susceptible to immune-mediated central (CNS) demyelination following infection by Theiler's murine encephalomyelitis virus (TMEV). SWR/J susceptibility is genetically dominant, when outcrossed to resistant H-2b strains. Non-H-2 differences between C57BL/6 and C57L/J (both H-2b) alter effects of 'susceptibility' genes, especially H-2q, from SWR/J. Genetic analysis of differential susceptibility to demyelination between SWR/J and C57L/J indicates that one copy of H-2q is sufficient for disease, and that SWR/J mice carry a non-H-2 gene which can lead to disease in the absence of H-2q. Differential susceptibility between SWR/J and C57BL/6 is determined by a single non-H-2 locus, which may or may not be the same as that differing between SWR/J and C57L/J.
Assuntos
Doenças Desmielinizantes/genética , Poliomielite/genética , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Suscetibilidade a Doenças , Feminino , Antígenos H-2/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fatores SexuaisRESUMO
We report differences among BALB/c substrains in susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, an immune-mediated inflammatory demyelinating disease and experimental model for human multiple sclerosis. BALB/cJ and BALB/cAnNCr mice are susceptible, while BALB/cByJ and BALB/cCum are resistant. Hybrids between BALB/cBy and BALB/cAnNCr were intermediate, although closer to the resistant parent. Backcrosses gave results compatible with differential susceptibility being related to a single segregating locus. Exposure of resistant BALB/cByJ mice to low dose irradiation, 2 days prior to infection, rendered them susceptible to TMEV-induced demyelination. The susceptibility pattern of TMEV-induced demyelinating disease among BALB/c substrains is distinct from those of several autoimmune disorders.
Assuntos
Doenças Desmielinizantes/genética , Theilovirus , Animais , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/imunologia , Suscetibilidade a Doenças , Teste de Histocompatibilidade , Camundongos , Camundongos Endogâmicos BALB C , Especificidade da EspécieRESUMO
Four horses were inoculated with Ehrlichia risticii contained in either infected murine P388 D1 cells or heparinized blood from an infected horse. All 4 horses produced serum antibody, plasma antigen, and clinical signs of the disease. An enzyme-linked immunosorbent assay was used to detect antibody in the serum and was also used in conjunction with an anti-E. risticii monoclonal antibody to detect antigenemia. These laboratory and clinical findings were correlated to determine the efficiency of the antigen detection method for discerning E. risticii infection.
Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Ehrlichiose/diagnóstico , Doenças dos Cavalos , Animais , Anticorpos Monoclonais , Ehrlichia/crescimento & desenvolvimento , Ehrlichiose/sangue , Ehrlichiose/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Cavalos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Camundongos , Células Tumorais CultivadasAssuntos
Regulação da Expressão Gênica , Proteínas da Mielina/genética , Células de Schwann/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Camundongos , Proteína P0 da Mielina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas S100/genética , Células de Schwann/citologiaRESUMO
The discovery that the dominant X-linked form of Charcot-Marie-Tooth disease (CMTX), a genetic disease of the peripheral nervous system (PNS), is associated with mutations in connexin32 (Cx32) has brought attention to the importance of connexins in glial cell biology. To gain further insight into the consequences of Cx32 deficiency, we have undertaken a detailed characterization of the gene expression profile of Schwann cells isolated from the sciatic nerve of wild-type and Cx32-null mice. Schwann cells exhibit two distinct phenotypes, myelinating and nonmyelinating, which are defined by their different morphology with respect to axons and by their unique profile of gene expression. Our findings show that, regardless of the mouse genotype, cultured Schwann cells express similar levels of messages for a number of connexins and for genes characteristic of both the myelinating and the nonmyelinating phenotypes. Furthermore, we have identified Cx36, a member of the gamma subclass of connexins, which are preferentially expressed in neuronal cells of mouse brain and retina, as an additional connexin present in Schwann cells. Mice lacking Cx32, however, exhibited a marked up-regulation of glial fibrillary acidic protein (GFAP), a cytoskeletal protein usually synthesized only by nonmyelinating Schwann cells. This observation was extended to the PNS in vivo and did not reflect a general perturbation of the expression of other nonmyelinating Schwann cell genes. These findings demonstrate that the absence of Cx32 results in a distinct pattern of gene dysregulation in Schwann cells and that Schwann cell homeostasis is critically dependent on the correct expression of Cx32 and not just any connexin. Identifying the relationship between increased GFAP expression and the absence of Cx32 could lead to the definition of specific roles for Cx32 in the control of myelin homeostasis and in the development of CMTX.
Assuntos
Conexinas/genética , Células de Schwann/fisiologia , Animais , Células Cultivadas , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/fisiopatologia , Primers do DNA , Expressão Gênica/fisiologia , Proteína Glial Fibrilar Ácida/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Bainha de Mielina/fisiologia , Fenótipo , Células de Schwann/citologia , Nervo Isquiático/citologia , Proteína beta-1 de Junções ComunicantesRESUMO
On intracerebral infection with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV), certain mouse strains develop a chronic demyelinating disease similar both clinically and pathologically to human multiple sclerosis. Other strains remain resistant. We previously established that differential susceptibility to this demyelinating disease exists among BALB/c substrains, with BALB/cAnNCr mice being susceptible while BALB/cByJ mice are resistant. BALB/cByJ mice are rendered susceptible to TMEV-induced demyelination on exposure to low dose gamma-irradiation before TMEV infection. BALB/cAnNCr and irradiated, infected BALB/cByJ animals are protected against TMEV-induced demyelination by the transfer of a splenic population from TMEV-infected BALB/cByJ donors. Resistance to demyelination appears to be mediated by a CD8+ radiosensitive population, which is induced on infection with TMEV and which must act early to establish resistance to TMEV-induced demyelination.
Assuntos
Linfócitos T CD8-Positivos/transplante , Imunoterapia Adotiva , Poliomielite/imunologia , Poliomielite/prevenção & controle , Theilovirus/imunologia , Animais , Linfócitos T CD8-Positivos/efeitos da radiação , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/prevenção & controle , Suscetibilidade a Doenças , Relação Dose-Resposta à Radiação , Tolerância Imunológica/efeitos da radiação , Imunidade Inata/efeitos da radiação , Camundongos , Camundongos Endogâmicos BALB C , Poliomielite/patologia , Baço/transplanteRESUMO
Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination and experimental allergic encephalomyelitis are the principal immunologically mediated, genetically controlled models of multiple sclerosis. Previous studies using different mapping techniques identified susceptibility loci for both diseases on chromosomes 3, 6, and 17. To more precisely map these TMEV and experimental allergic encephalomyelitis loci relative to each other, linkage analysis using microsatellite markers and a (BALB/cByJ x DBA/2J) x BALB/cByJ backcross population segregating for TMEV-induced disease was conducted. Comparisonwise and chromosomewise critical values based on permutation theory were estimated for each chromosome. Evidence for linkage to markers on chromosome 17 was not seen. Chromosomewise linkage (p = 0.13) was detected with D6 Mit36 and D6 Mit149 (marker-specific chromosomewise p values = 0.02) at 40.4 cM on chromosome 6. Chromosomewise linkage (p < 0.01) (marker-specific chromosomewise p value = 0.0) and comparisonwise linkage (p < < 0.0001) to D3 Mit156 at 33.9 cM on chromosome 3 were observed along with chromosomewise linkage (p < 0.05) and comparisonwise linkage (p < < 0.0001) to D3 Mit29, D3 Mit311, D3 Mit28, and D3 Mit11 from 33.9 to 37.2 cM, respectively. Significant linkage to D3 Mit156 places Tmevd2 1.1 cM proximal of D3 Mit101 (35 cM), the maximally linked marker to the eae3 susceptibility gene. Maximum likelihood estimates conducted by multilocus linkage analysis localized Tmevd2 within a 95% confidence interval bordered by D3 Mit29 and D3 Mit10, at 33.9 and 37.2 cM, respectively. Taken together these results suggest that Tmevd2 and eae3 may represent either a single, common susceptibility gene or members of a gene complex involved in central nervous system immunopathology.
Assuntos
Doenças Desmielinizantes/genética , Doenças Desmielinizantes/imunologia , Encefalomielite Autoimune Experimental/genética , Regulação da Expressão Gênica/imunologia , Theilovirus/genética , Animais , Mapeamento Cromossômico , Suscetibilidade a Doenças , Encefalomielite Autoimune Experimental/imunologia , Feminino , Ligação Genética , Marcadores Genéticos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Poliomielite/genética , Poliomielite/imunologiaRESUMO
Selection of potential cardiac recipients is not a simple process. Identification of patients who are declining from end-stage cardiac disease and may be expected to die within 12 months or less and deciding which of a number of cardiac invalids are reasonable candidates for cardiac transplantation involves prognostication as well as a working knowledge of the expected benefits and survival rates in cardiac transplantation. Screening by means of the currently accepted contraindications for cardiac transplantation is somewhat more difficult in 1986 than it was 10 years ago when these contraindications were changing less rapidly. However, for optimal use of the limited supply of donor organs and maintenance of reasonable survival rates such screening is absolutely necessary. A second area of restriction that is less approachable by the physician is that of financial limitations. It would appear that the working poor and lower middle class may be deprived of the opportunity for cardiac transplantation much as they are deprived of the opportunity for optimal medical care in our society today.