Biomedical subjects

G Consalez

Publications and source records attributed to G Consalez.

5 recordsLinked to original sources

PubMed2006

Cerebellar neurons and glial cells are transducible by lentiviral vectors without decrease of cerebellar functions.

Due to the profuse connections of the cerebellum to the rest of the central nervous system, cerebellar dysfunction impacts tremendously on movement coordination, maintenance of equilibrium, muscle tone and motor memory. Efficient gene transfer of therapeutic genes to this central nervous system structure would constitute a relevant step ahead the design of treatments to ameliorate cerebellar dysfunction. Lentiviral vectors (LVs) have been used as efficient vehicles to integrate transgenes into dividing and non-dividing cells, such as postmitotic adult neurons, with minimal toxicity and immune response. This study aimed to use LVs carrying green fluorescent protein (GFP) cDNA for transduction of cerebellar cells in vivo without compromising neurological cerebellar functions. Our results indicate that LVs, injected in the lobulus simplex, transduced different cerebellar neurons including stellate, Purkinje cells, granular neurons and glial cells such as astrocytes, oligodendrocytes, and that this gene transfer approach was not accompanied by cerebellar deficits.

Animals↗

PubMed1999

ZFM1/SF1 mRNA in rat and gerbil brain after global ischaemia.

Cerebral ischaemia results in significant brain damage, but the molecular mechanisms associated with ischaemia-induced brain injury are not well defined. We have adopted an improved differential-display method to search for new ischaemia-related genes. Among the different cDNAs isolated following transient forebrain ischaemia in rat, PH3.3 was selected for further studies. The search for homologies revealed that it is the rat homologue to human zinc finger motif 1 (ZFM1), also called mammalian splicing factor 1 (SF1). With Northern blot, PH3.3 hybridized with three mRNA species of 2.3, 2.9 and 3.6 kb, significantly increased at 6 h and 5 days after the ischaemic insult. These findings were extended also to another animal model. In situ hybridization in ischaemic gerbils showed that PH3.3 mRNA was induced in the dentate gyrus as early as 4 h post-ischaemia. Expression peaked at 2 days in the whole hippocampus and cortex, and then progressively decreased towards sham levels. By day 4, expression had disappeared almost entirely from the cells in the CA1 region of the hippocampus, concomitant with the degeneration of pyramidal neurons. Interestingly, ZFM1/SF1 has been recently identified as activated following p53-induced apoptosis. Several lines of evidence suggest that p53 may play two roles in the post-ischaemic brain. The primary role of p53 is to activate DNA repair processes, but if repair fails, apoptosis will be initiated. Thus, ZFM1/SF1 may represent a relevant link between p53 and the neuroprotective/neurodegenerative processes which follow cerebral ischaemia.

Amino Acid Sequence↗

PubMed1998

Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region.

Eukaryotic protein kinases are part of a large and expanding family of proteins. Through our transcriptional mapping effort in the Xp22 region, we have isolated and sequenced the full-length transcript of STK9, a novel cDNA highly homologous to serine-threonine kinases. A number of human genetic disorders have been mapped to the region where STK9 has been localized including Nance-Horan (NH) syndrome, oral-facial-digital syndrome type 1 (OFD1), and a novel locus for nonsyndromic sensorineural deafness (DFN6). To evaluate the possible involvement of STK9 in any of the above-mentioned disorders, a 2416-bp full-length cDNA was assembled. The entire genomic structure of the gene, which is composed of 20 coding exons, was determined. Northern analysis revealed a transcript larger than 9.5 kb in several tissues including brain, lung, and kidney. The mouse homologue (Stk9) was identified and mapped in the mouse in the region syntenic to human Xp. This location is compatible with the location of the Xcat mutant, which shows congenital cataracts very similar to those observed in NH patients. Sequence homologies, expression pattern, and mapping information in both human and mouse make STK9 a candidate gene for the above-mentioned disorders.

Amino Acid Sequence↗

PubMed1994

Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3.

Several human inherited diseases have been localized to the Xq13.3 region of the human X chromosome (X-linked dystonia with Parkinsonism, sideroblastic anemia, SCID, Menkes disease and X-linked mental retardation loci). Genes involved in the phenotypes have been isolated for only two of them (Menkes and SCIDX). It was therefore interesting to isolate and characterize new genes from the region. In a previous work (12 and Consalez et al, in preparation) we isolated a gene (XNP), located 350 Kb proximal to PGK1, potentially coding for a nuclear protein. We describe here the cloning and characterization of the murine homologue. The pattern of expression of the gene in the newborn mouse (especially the expression in particular regions of the brain: optical lobe, frontal cortex, hippocampus and cerebellum), as well as the expression in human tissues, suggests that this gene might be involved in neuronal differentiation. Among the different morbid phenotypes assigned to the region, X-linked mental retardation would be the best candidate to be associated with this gene.

Amino Acid Sequence↗

PubMed1992

Genetic variants of alpha-1-antitrypsin (AAT).

This paper reviews the genetic variants of alpha-1-antitrypsin (AAT) which have been sequenced with special emphasis on the s.c. deficiency variants. These result in AAT low plasma levels via three main mechanisms: 1) intracellular storage; 2) intracellular degradation; 3) lack of synthesis. Intracellular storage occurs with the classical Z variant and with a few variants called M-like, because of their isoelectric focusing (IF) pattern. The storage phenomenon causes liver damage and can be demonstrated at both light and electron microscopic level with the help of immunohistochemistry. We report a new deficiency variant of AAT (M-Cagliari) characterized by very low plasma levels, massive storage of AAT and liver cirrhosis. By using immunohistochemical techniques and DNA analysis we could demonstrate that M-Cagliari has antigenic and genetic properties other than the Z AAT.

Base Sequence↗