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Biomedical subjects

M Janitz

Publications and source records attributed to M Janitz.

9 recordsLinked to original sources
PubMed1998

Three alternatively spliced variants of the gene coding for the human bone morphogenetic protein-1.

The human bone morphogenetic protein-1 was originally identified as a protein with the capacity to stimulate bone and cartilage growth in vitro. Its gene sequence identified it as an alternatively spliced human homolog of the Drosophila dorsal-ventral patterning tolloid gene and suggested that it activates transforming growth factor-beta-like molecules by proteolytic cleavage. Its expression pattern and its recently identified activity as a procollagen C proteinase, however, suggest that it has a more general function in the early stages of embryogenesis. This view is strengthened by the previous observation of a third alternatively spliced isoform of the gene, called bone morphogenetic protein 1/His. We now show that the gene is expressed in three additional variants, leading to shorter and slightly modified C-termini. The three variants are preferentially expressed in placenta but show individual differences in their expression profiles in other soft tissues.

Alternative Splicing↗
PubMed1998

Expression of the H2-Ea gene is modulated by a polymorphic transcriptional enhancer.

In all vertebrates the major histocompatibility complex (MHC) class II genes are polymorphic in their coding regions as well as in their promoter control elements. This polymorphism correlates with a variability in peptide binding and a variability in transcriptional activities. There is, however, one exception to this rule, which is the mouse H2-Ea gene or the corresponding human DRA gene. So far and for unkown reasons no polymorphism has been observed in these loci. We sequenced the distal transcriptional control elements of the H2-Ea, H2-Eb, and H2-Ab genes from the mouse haplotypes H2d, H2k, H2q, and H2z, and in contrast to the promoter and coding regions a sequence polymorphism can be detected which is limited to the H2-Ea gene. In transfection experiments this polymorphism can be seen to influence haplotype-specifically the transcriptional activities in B cells. This finding strongly suggests an evolutionary pressure towards a haplotype-specific expression pattern in all four MHC class II genes. The genetic differences in control elements of MHC class II genes may well contribute to differential immune reactivities and to immune disorders like allergies or autoimmune diseases.

Amino Acid Sequence↗
PubMed1998

The distribution of variation in regulatory gene segments, as present in MHC class II promoters.

Diversity in the antigen-binding receptors of the immune system has long been a primary interest of biologists. Recently it has been suggested that polymorphism in regulatory (noncoding) gene segments is of substantial importance as well. Here, we survey the level of variation in MHC class II gene promoters in man and mouse using extensive collections of published sequences together with unpublished sequences recently deposited by us in the EMBL gene bank using the Shannon entropy to quantify diversity. For comparison, we also apply our analysis to distantly related MHC class II promoters, as well as to class I promoters and to class II coding regions. We observe a high level of intraspecies variability, which in mouse but not in man is localized to a significant extent near the binding sites of transcription factors-sites that are conserved over longer evolutionary distances. This localization may both indicate and enhance heterozygote advantage, as the presence of two functionally different promoters would be expected to confer flexibility in the immune response.

Animals↗
PubMed1997

Polymorphic MHC class II promoters exhibit distinct expression pattern in various antigen-presenting cell lines.

The promoter regions of MHC class II genes are characterized by the presence of conserved sequence motifs called S,X and Y boxes, which are crucial for regulation of transcription of these genes. In humans, promoter polymorphism is known to result in differential transcriptional activity at both inter-locus and inter-allelic levels, but it is not yet known how this relates to tissue-specific expression of MHC class II molecules. We sequenced the 5' regulatory regions of alpha and beta genes of I-A and I-E molecules from four mouse haplotypes and found allelic polymorphisms which were mainly confined to the X box. The promoter sequences of I-Ea genes were non-polymorphic. Transfection of four antigen-presenting cell types with promoter-reporter gene constructs revealed that the promoter sequence polymorphisms result in distinct allele- and tissue-specific activity patterns. Mutagenesis experiments in which the X2 box was reshuffled between I-A beta alleles demonstrated that this box contributes to regulation of differential MHC class II expression in the four cell types. The possibility is discussed that tissue-specific MHC class II expression may control differentiation of T-cell subsets.

Animals↗
PubMed1995

Analysis of mRNA expression for interleukin-1 genes on human testicular cells.

We have investigated mRNA expression for IL-1 alpha and IL-1 beta gene on fractionated human testicular cells. Using RT-PCR and Northern blot hybridization technique we detected the presence of IL-1 alpha transcripts, predominantly in the intratubular compartment of the testis, comprising gametogenic and Sertoli cells. We were also able to detect mRNA for IL-1 alpha on the testicular interstitium, but at significantly lower levels. The intertubular compartment of the testis, mainly consisting of macrophages and Leydig cells, appeared however, to be a site for IL-1 beta gene expression. Our experimental data confirm previous results obtained in animal models indicating that the testis is capable of producing interleukin-1 under physiological conditions. Testicular IL-1 may function as a tissue-specific factor modulating both spermato- and steroidogenic activity of human testis.

Base Sequence↗
PubMed1994

Analysis of mRNA for class I HLA on human gametogenic cells.

We have studied mRNA expression for Class I HLA (human leukocyte antigen) on male germ cells by amplification of gene fragments in PCR technique and by Northern hybridization. RNA was extracted from fractionated gametogenic cells (isolated from testis) and reversely transcribed. Then, cDNA was amplified for specific HLA sequence (HLA, -A, -B, -C). The specificity of this product was confirmed in "nested" PCR of 400 bp gene fragment coding for alpha 2 domain, alpha 3 domain, and the transmembrane portion of Class I HLA. The results indicate minimal expression of classical Class I HLA on gametogenic cells. Northern hybridization with 669 bp cDNA fragment (spanning for alpha 3 domain, transmembrane, cytoplasmic, and 3' untranslated region) resulted in a low intensity signal from gametogenic cell fractions and confirmed our findings obtained by PCR. The minimal expression of classical HLA antigens may create a neutral cover for the male reproductive system, thereby preventing an immunological response during germ cell differentiation.

Blotting, Northern↗
PubMed1993

In situ localization of HLA class I mRNA in human testis.

We have used a 0.35-kilobase (kb) antisense RNA probe complementary to the monomorphic regions of both classical and nonclassical HLA class I sequences to detect histocompatibility-class-I-antigen-specific mRNA in human testicular tissue. The message has been clearly detected in the interstitium while less intensive staining was revealed in the peribasal compartment of the seminiferous epithelium.

Antisense Elements (Genetics)↗