RESUMO
Unprecedented cure after infection with the lethal Plasmodium berghei ANKA was observed in an F2 progeny generated by intercrossing the wild-derived WLA and the laboratory C57BL/6 mouse strains. Resistant mice were able to clear parasitaemia and establish immunity. The observed resistance was disclosed as a combinatorial effect of genetic factors derived from the two parental strains. Genetic mapping of survival time showed that the WLA allele at a locus on chromosome 1 (colocalizing with Berghei resistance 1 (Berr1), a locus associated with resistance to experimental cerebral malaria) increases the probability to resist early death. Also, the C57Bl/6 allele at a novel locus on chromosome 9 (Berr3) confers overall resistance to this lethal Plasmodium infection. This report underlines the value of using wild-derived mouse strains to identify novel genetic factors in the aetiology of disease phenotypes, and provides a unique model for studying parasite clearance and immunity associated with malaria.
Assuntos
Cromossomos/genética , Imunidade Inata/genética , Malária/genética , Plasmodium berghei , Locos de Características Quantitativas/genética , Animais , Mapeamento Cromossômico , Predisposição Genética para Doença/genética , Malária/imunologia , Malária/parasitologia , Camundongos , Plasmodium berghei/imunologia , Locos de Características Quantitativas/imunologiaAssuntos
Antirreumáticos/administração & dosagem , Metotrexato/administração & dosagem , Espondilite Anquilosante/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Antirreumáticos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Probabilidade , Valores de Referência , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico , Resultado do Tratamento , Reino UnidoRESUMO
The neurological syndrome caused by Plasmodium berghei ANKA in rodents partially mimics the human disease. Several rodent models of cerebral malaria (CM) exist for the study of the mechanisms that cause the disease. However, since common laboratory mouse strains have limited gene pools, the role of their phenotypic variations causing CM is restricted. This constitutes an obstacle for efficient genetic analysis relating to the pathogenesis of malaria. Most common laboratory mouse strains are susceptible to CM, and the same major histocompatibility complex (MHC) haplotype may exhibit different levels of susceptibility. We analyzed the influence of the MHC haplotype on overcoming CM by using MHC congenic mice with C57BL/10 and C3H backgrounds. No correlation was found between MHC molecules and the development of CM. New wild-derived mouse strains with wide genetic polymorphisms were then used to find new models of resistance to CM. Six of the twelve strains tested were resistant to CM. For two of them, F(1) progeny and backcrosses performed with the reference strain C57BL/6 showed a high level of heterogeneity in the number and characteristics of the genetic factors associated with resistance to CM.
Assuntos
Malária Cerebral/imunologia , Plasmodium berghei , Animais , Suscetibilidade a Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Especificidade da EspécieRESUMO
Some IVF laboratories ask for donor's semen during an ICS attempt if retrieval of husband's sperm is unsuccessful. The French Centers for Semen preservation (CECOS) consider that this request is not acceptable for legal, psychological and ethical considerations. Legal consent may not be ambiguous. The psychological lost of biological fatherhood should be totally assumed before undertaking conception with donor's semen. ICSI should be started only if it is most likely to succeed. For all these reasons, CECOS refuse to modify the strategy of procreatione during the course of an attempt.