The (Na+ + K+)-ATPase activity in brain of Quaking mice.

The (Na+ 4 K+)- and Mg2+-dependent ATPase distribution in several brain areas has been investigated in Quaking mutant mice characterized by myelin deficiency. A marked decrease of (Na+ + K+)-ATPase activity has been found in limbic structures, hypothalamus and cerebellum. The Mg2+-dependent activity did not change. A possible involvement of the impairment of the (Na+ + K+)-ATPase activity in the seizure susceptibility of this mice is discussed.     

Implication of phosphoinositide phosphatases in genetic diseases: the case of myotubularin

Phosphoinositides play a central role in the control of major eukaryotic cell signaling mechanisms. Accordingly, the list of phosphoinositide-metabolizing enzymes implicated in human diseases has considerably increased these last years. Here we will focus on myotubularin, the protein mutated in the X-linked myotubular myopathy (XLMTM) and the founding member of a family of 13 related proteins. Recent data demonstrate that myotubularin and several other members of the family are potent lipid phosphatases showing a marked specificity for phosphatidylinositol 3-phosphate [PtdIns(3)P]. This finding has raised considerable interest as PtdIns(3)P is implicated in vesicular trafficking and sorting through its binding to specific protein domains. The structure of myotubularin, the molecular mechanisms of its function and its implication in the etiology of XLMTM will be discussed, as well as the potential function and role of the other members of the family.Received 14 February 2003; received after revision 10 April 2003; accepted 14 April 2003     

Differentiation of dissociated neurons from chick embryo cerebral hemispheres cultivated inRose chambers with and without cellophane membrane

Zusammenfassung Dissoziierte Nervenzellen der Gehirnhemisphären von Hühnerembryonen wurden inRose-Kammern mit und ohne Cellophanmembran kultiviert. Die Differenzierung der Neurone wurde mit Phasenkontrast und histochemischen Methoden untersucht.

---

---

Chargée de Recherche au CNRS.     

The effect of pulsating electrical current on isolated nerve cells from the chick cerebral hemispheres cultivated in the rose chamber

Summary It was shown that 73% of the fusiform cells obtained in short-term cultures of dissociated cerebral hemispheres of the chick embryo become oriented under the effect of a pulsating current, applied during the first 24 h of culture.Maître de Recherche au CNRS     

Glutamate decarboxylase activity in brain regions of differentially-housed mice; a difference in the olfactory bulb

Summary Glutamate decarboxylase (GAD) activities were determined in homogenates of 8 brain regions of mice that had been differentially housed (isolated vs grouped) for 4–9 weeks. GAD activity was lower in whole forebrains and in olfactory bulbs of isolated mice, changes which might be associated with their increased aggressiveness.     

Etude de l'activité adénosinetriphosphatasique et hexokinasique de cristallins de lapins soumis à une irradiation locale par les rayons X

Summary The irradiation of the lens by a simple dose of 1400 r, gives a very important and lasting reduction of its hexokinase activity. Its ATPase activity shows an increase during the first four days and a return to normal again. The variations observed here (that isin vivo) are different from the ones noted after irradiation of these enzymesin vitro.

---

---

Travail effectué avec le concours matériel de l'Institut National d'Hygiène.     

Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.

Thiamine-responsive megaloblastic anaemia (TRMA), also known as Rogers syndrome, is an early onset, autosomal recessive disorder defined by the occurrence of megaloblastic anaemia, diabetes mellitus and sensorineural deafness, responding in varying degrees to thiamine treatment (MIM 249270). We have previously narrowed the TRMA locus from a 16-cM to a 4-cM interval on chromosomal region 1q23.3 (refs 3,4) and this region has been further refined to a 1.4-cM interval. Previous studies have suggested that deficiency in a high-affinity thiamine transporter may cause this disorder. Here we identify the TRMA gene by positional cloning. We assembled a P1-derived artificial chromosome (PAC) contig spanning the TRMA candidate region. This clarified the order of genetic markers across the TRMA locus, provided 9 new polymorphic markers and narrowed the locus to an approximately 400-kb region. Mutations in a new gene, SLC19A2, encoding a putative transmembrane protein homologous to the reduced folate carrier proteins, were found in all affected individuals in six TRMA families, suggesting that a defective thiamine transporter protein (THTR-1) may underlie the TRMA syndrome.     

Amnionless,essential for mouse gastrulation,is mutated in recessive hereditary megaloblastic anemia

The amnionless gene, Amn, on mouse chromosome 12 encodes a type I transmembrane protein that is expressed in the extraembryonic visceral layer during gastrulation. Mice homozygous with respect to the amn mutation generated by a transgene insertion have no amnion. The embryos are severely compromised, surviving to the tenth day of gestation but seem to lack the mesodermal layers that normally produce the trunk. The Amn protein has one transmembrane domain separating a larger, N-terminal extracellular region and a smaller, C-terminal cytoplasmic region. The extracellular region harbors a cysteine-rich domain resembling those occurring in Chordin, found in Xenopus laevis embryos, and Sog, found in Drosophila melanogaster. As these cysteine-rich domains bind bone morphogenetic proteins (Bmps), it has been speculated that the cysteine-rich domain in Amn also binds Bmps. We show that homozygous mutations affecting exons 1-4 of human AMN lead to selective malabsorption of vitamin B12 (a phenotype associated with megaloblastic anemia 1, MGA1; OMIM 261100; refs. 5,6) in otherwise normal individuals, suggesting that the 5' end of AMN is dispensable for embryonic development but necessary for absorption of vitamin B12. When the 5' end of AMN is truncated by mutations, translation is initiated from alternative downstream start codons.