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.     

Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic beta cells

A class I histocompatibility gene, H-2Kb, linked to the rat insulin promoter, is overexpressed in the pancreatic beta cells of transgenic mice. The mice, whether syngeneic or allogeneic to the transgene, develop insulin dependent diabetes without detectable T cell infiltration, suggesting a direct, non-immune role for the transgenic class I molecules in the disease process.     

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     

Hybridization of mitochondrial and cytoplasmic ribosomal RNA with mitochondrial and nuclear DNA.

Hybridization assays of rat liver mitochondrial and cytoplasmic rRNAs with in vitro labelled mitochondrial and nuclear DNA were performed in liquid medium. Sensitivity towards S1 enzyme and Tms of the RNA-DNA hybrids were studied. Our results are in favour of a distinct genetic origin of the two types of cellular rRNAs.     

The relative distribution of soluble and insoluble cholinesterases in rat excitable tissues

Summary Three ratios were studied here: bound to free AChE (R₁), bound to free BChE (R₂), and the ratios between these two (R₃). The first one proved relevant in that it contributed to the division of the cholinergic tissues into 3 classes: high values (nicotinic tissues: skeletal muscle), low values(muscarinic tissues: small intestine, uterus, heart), and middle values (mixed, nicotinic and muscarinic cholinergic innervation:brain). The third ratio (R₃) showed different values in the muscarinic tissues studied; no significant differences could, however, be found between the ratios of brain and skeletal muscle. Further exploration of this ratio should indicate whether it is of some importance for the characterization of excitable tissues.     

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.     

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.