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D Bächner

Publications and source records attributed to D Bächner.

23 records · Page 2Linked to original sources
PubMed1995

Expression patterns of two human genes coding for different rab GDP-dissociation inhibitors (GDIs), extremely conserved proteins involved in cellular transport.

We have analysed the expression patterns of two human genes coding for two different rab GDIs, rab GDI alpha/XAP-4 and rab GDI beta, proteins involved in the regulation of vesicle-mediated cellular transport. The gene sequences are extremely conserved in evolution, with substantial homology preserved across three eukaryotic kingdoms. Although the sequence homology between the two human rab GDIs studied is very high, their expression patterns are completely different. The Northern blot analysis and in situ hybridization to sections of mouse embryos and postnatal tissues have revealed that the rab GDI alpha/XAP-4 is expressed predominantly in neural and sensory tissues and may thus serve a specific function in neural signal transmission. In contrast to rab GDI alpha/XAP-4, the human rab GDI beta is expressed ubiquitously.

Amino Acid Sequence↗
PubMed1995

Structural organization and developmental expression pattern of the mouse WD-repeat gene DMR-N9 immediately upstream of the myotonic dystrophy locus.

The diverse biological consequences of size-expansion of the unstable (CTG)n repeat in the myotonic dystrophy protein kinase (DM-PK) gene at chromosome region 19q13.3, are still poorly understood. Abnormal (CTG)n length may affect either DM-PK mRNA fate or function, or alternatively, compromise gene transcription by distortion of chromatin configuration. In the latter model involvement of neighbouring genes in DM upon extreme expansion of the repeat cannot be discarded as a possibility and should be studied further. Here we report on the elucidation of the complete genomic structure and expression pattern of the mouse DMR-N9 gene (called 59 gene in humans), which is at 1.1 kbp upstream of the DM-PK gene. This gene contains five exons spanning 7 kbp and codes for a protein of 650 amino acids. Two regions of the predicted protein show significant homology to WD repeats, highly conserved amino acid sequences found in a family of proteins engaged in signal transduction or cell regulatory functions. The start site of transcription has been determined and we have identified putative transcription factor binding sequences in a 400 bp putative promoter area immediately upstream of the transcribed unit. Northern blotting analysis and RNA in situ hybridization revealed ubiquitous low expression in all tissues of the mouse embryo and enhanced expression in adult brain and testis. The onset of transcription is phased early in mouse embryogenesis, before or at day 9.5 of gestation. From day 14.5 onwards DMR-N9 mRNAs were detected in all neural tissues, especially in the telencephalon and mesencephalon. Later, mRNA presence is evident in distinct tubules of the mature testis, restricted to secondary spermatocytes of stages VIII to XII of the spermatogenic proliferation cycle. We conclude that the DMR-N9 gene is a candidate for being involved in the manifestation of mental and testicular symptoms in severe cases of DM.

Amino Acid Sequence↗
PubMed1995

Expression of the Huntington disease gene in rodents: cloning the rat homologue and evidence for downregulation in non-neuronal tissues during development.

Huntington's disease (HD) is associated with an expanded and unstable (CAG) > 35 repeat within a gene of unknown function. We isolated the complete coding region of the rat HD gene (rhd) from cDNA libraries and investigated its expression in different developmental stages of rodent tissues. The rat gene exhibits 90% peptide sequence identity to the human and 96% to the murine sequence. The (CAG)n repeat is markedly reduced in the rat compared to the average human (CAG)n block. Northern blot analysis and in situ hybridizations reveal that in rodents the hd gene is already expressed during embryonal development. As in humans, the rhd gene is expressed in two transcriptional isoforms which result from different polyadenylation signals. In mice, however, a third transcript of intermediate size was found predominantly expressed in brain. This transcript is downregulated in later development. At day 14.5 p.c. the level of rhd expression is similar in the brain and in non-neuronal tissues. In contrast, the expression in non-neuronal tissues is markedly reduced in adult animals and corresponds to the restricted distribution of neuropathologic changes observed in HD patients.

Amino Acid Sequence↗
PubMed1993

Enhanced expression of the murine FMR1 gene during germ cell proliferation suggests a special function in both the male and the female gonad.

To elucidate the function of the FMR1 gene, we applied RNA in situ hybridization to cryosections of mice from different developmental stages. The murine Fmr-1 was found transcribed in a ubiquitous manner with an expression pattern similar to glyceraldehyd phosphate dehydrogenase, Gapdh, which was used as a control gene. A significant difference in the Fmr-1 expression pattern, however, was markedly enhanced expression specifically confined to the testis and the fetal ovary. In the immature and mature testis an elevated level of Fmr-1 expression is found in type A1 spermatogonia. Expression in the testis is observed in fetal life, reaches the highest level in the immature testis, and declines early in adult life. In the mature ovary no specific Fmr-1 expression signal was found but enhanced levels were seen in the fetal ovary. At this developmental stage proliferation of oogonia takes place. It is suggested that FMR1 serves a special function during germ cell proliferation in males and females. These findings are discussed in the light of the current observation that fragile X patients produce only sperm with a premutation sized allele. Two hypotheses are put forward: (1) In males lack of FMR1 function results in a premeiotic defect preventing spermatogonia with a full mutation to reach meiosis. A fragile X mutation can be passed on to offsprings only as a premutation (selection hypothesis). (2) Transition of a premutation allele to full mutation occurs in a postzygotic stage after separation of the germ line and is restricted to soma cells (restriction hypothesis). Expression of FMR1 in proliferating germ cells is in line with both hypothesis.

Aging↗