Spleen-specific Expression of the Malaria-inducible Intronless Mouse Gene imap38

Krücken, Jürgen; Stamm, Olaf; Schmitt-Wrede, Hans-Peter; Mincheva, Antoaneta; Lichter, Peter; Wunderlich, Frank

doi:10.1074/jbc.274.34.24383

Cited by 33 publications

(41 citation statements)

References 57 publications

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“…Three members of this gene family have been described: Ian1 is a thymic selection marker expressed at various stages of thymocyte development (28). Ian2 is induced in B-lymphocytes by infections of Plasmodium chabaudi malaria (29,30). Ian3 (28) has not been functionally characterized.…”

Section: Resultsmentioning

confidence: 99%

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

Hornum¹,

Rømer

Markholst³

2002

Diabetes

152

143

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1Diabetes-prone (DP) BB rats spontaneously develop insulin-dependent diabetes resembling human type 1 diabetes. They also exhibit lifelong T-cell lymphopenia. Functional and genetic data support the hypothesis that the gene responsible for the lymphopenia, Lyp, is also a diabetes susceptibility gene, named Iddm1. We constructed a 550-kb P1-derived artificial chromosome contig of the region. Here, we present a corrected genetic map reducing the genetic interval to 0.2 cM and the physical interval to 150 -290 kb. A total of 13 genes and six GenomeScan models are assigned to the homologous human DNA segment on HSA7q36.1, 8 of which belong to the family of immune-associated nucleotides (Ian genes). Two of these are orthologous to mouse Ian1 and -4, both excellent candidates for Iddm1. In normal rats, they are expressed in the thymus and T-cell regions of the spleen. In the thymus of lymphopenic rats, Ian1 exhibits wild-type expression patterns, whereas Ian4 expression is reduced. Mutational screening of their coding sequences revealed a frameshift mutation in Ian4 among lymphopenic rats. The mutation results in a truncated protein in which the COOH-terminal 215 amino acids-including the anchor localizing the protein to the outer mitochondrial membrane-are replaced by 19 other amino acids. We propose that Ian4 is identical to Iddm1.

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Section: Resultsmentioning

confidence: 99%

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

Hornum¹,

Rømer

Markholst³

2002

Diabetes

152

143

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“…Detection of the single-copy genomic mouse imap38 gene served as a DNA loading control (31). When quantified relative to imap38, the level of adenovirus DNA in the livers of mice infected with the different viruses was found to be roughly equivalent at day 4 postinfection (Fig.…”

Section: Inhibition Of Preexisting Hbv Gene Expression In the Liver Omentioning

confidence: 99%

Clearance of hepatitis B virus from the liver of transgenic mice by short hairpin RNAs

Uprichard

Boyd

Althage

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

185

135

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Hepatitis B virus (HBV) causes acute and chronic hepatitis and hepatocellular carcinoma. Although a preventive vaccine is available, the therapeutic options for chronically infected patients are limited. It has been shown that RNA interference can prevent HBV gene expression and replication in vivo when HBV expression vectors are delivered simultaneously with small interfering RNA (siRNA) or siRNA expression constructs. However, the therapeutic potential of siRNAs to interrupt ongoing HBV replication in vivo has not been established. Here, we show that expression of HBVspecific siRNAs in the liver of HBV transgenic mice by recombinant adenoviruses can suppress preexisting HBV gene expression and replication to almost undetectable levels for at least 26 days. These results demonstrate that efficiently delivered siRNAs should be able to silence HBV in chronically infected patients.adenovirus vector ͉ RNA interference C hronic hepatitis B virus (HBV) infection causes Ͼ1 million deaths each year due to cirrhosis of the liver and hepatocellular carcinoma (www.cdc.gov͞hepatitis and www.who.int͞ mediacentre͞factsheets͞fs204͞en). Hence, there is a need for alternative ways to treat this persistent infection. RNA interference (RNAi) has rapidly emerged as a technology for regulating mammalian gene expression because it provides a means of sequence-directed degradation of specific RNAs (1-8). In the case of HBV, published in vivo hydrodynamic transfection studies have shown that simultaneous delivery of HBV expression plasmids and HBV-specific small interfering RNAs (siRNAs) (or siRNA-expressing constructs) to the mouse liver can prevent the induction of HBV gene expression and replication (9-11). To expand on those studies, we have examined the therapeutic potential of RNAi for the treatment of chronic HBV infection where ongoing viral gene expression and replication are established in the liver before siRNA delivery.Several variables that have not been previously addressed could affect the utility of RNAi for the treatment of an ongoing HBV infection. First, in the context of an established infection, viral RNAs may be protected within complexes or nucleocapsid structures as has been reported for hepatitis D virus (1), Rous sarcoma virus (12), and respiratory syncytial virus (RSV) (13). This is particularly relevant to HBV, which replicates in capsids after encapsidation of the viral pregenomic RNA. A second variable is how efficiently preexisting viral RNA can be reduced and to what extent RNA suppression can block viral DNA replication. Finally, established viral gene expression may allow for the induction of viral RNAi-defense mechanisms as reported for plant viruses (14) and flockhouse nodavirus (15).It has been shown that RNAi is capable of reducing mammalian gene expression in vivo. Genes such as fas (16), caspase-8 (17), agouti-related peptide (18), tyrosine hydroxylase (19), and ras (20, 21) have been targeted for degradation in mice, and corresponding changes in phenotype were observed. Yet, the actual degree o...

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“…Furthermore, testosterone-induced susceptibility appears to be due to hormonal imprinting, as testosterone treatment of female mice for 3 weeks followed by 9 weeks without treatment, during which time testosterone falls to pretreatment levels, continues to make female mice susceptibile to challenge with P. chabaudi (19). Recently, a novel putative transmembrane protein (IAP30) which is induced on murine spleen cells during P. chabaudi infection in the presence of testosterone has been identified (75,76). The importance of gender-influenced susceptibility to P. chabaudi is emphasized in experiments that demonstrate that the efficacy of vaccination against this parasite is as high as 90% in female mice but only 55% in males.…”

Section: Plasmodiummentioning

confidence: 99%

Sex-Associated Hormones and Immunity to Protozoan Parasites

2001

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Numerous epidemiological and clinical studies have noted differences in the incidence and severity of parasitic diseases between males and females. Although in some instances this may be due to gender-associated differences in behavior, there is overwhelming evidence that sex-associated hormones can also modulate immune responses and consequently directly influence the outcome of parasitic infection. Animal models of disease can often recreate the gender-dependent differences observed in humans, and the role of sex-associated hormones can be confirmed by experimentally altering their levels. Under normal circumstances, levels of sex hormones not only differ between males and females but vary according to age. Furthermore, not only are females of reproductive age subject to the regular hormonal cycles which control ovulation, they are also exposed to dramatically altered levels during pregnancy. It is thus not surprising that the severity of many diseases, including those caused by parasites, has been shown to be affected by one or more of these circumstances. In addition, infection with many pathogens has been shown to have an adverse influence on pregnancy. In this article we review the impact of sex-associated hormones on the immune system and the development and maintenance of immunity to the intracellular protozoan parasites Toxoplasma gondii, Plasmodium spp., and Leishmania spp

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Spleen-specific Expression of the Malaria-inducible Intronless Mouse Gene imap38

Cited by 33 publications

References 57 publications

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

The Diabetes-Prone BB Rat Carries a Frameshift Mutation inIan4, a Positional Candidate ofIddm1

Clearance of hepatitis B virus from the liver of transgenic mice by short hairpin RNAs

Sex-Associated Hormones and Immunity to Protozoan Parasites

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