Vasotocin neurons and septal V1a-like receptors potently modulate songbird flocking and responses to novelty.

Previous comparisons of territorial and gregarious finches (family Estrildidae) suggest the hypothesis that arginine vasotocin (VT) neurons in the medial bed nucleus of the stria terminalis (BSTm) and V(1a)-like receptors in the lateral septum (LS) promote flocking behavior. Consistent with this hypothesis, we now show that intraseptal infusions of a V(1a) antagonist in male zebra finches (Taeniopygia guttata) reduce gregariousness (preference for a group of 10 versus 2 conspecific males), but have no effect on the amount of time that subjects spend in close proximity to other birds ("contact time"). The antagonist also produces a profound increase in anxiety-like behavior, as exhibited by an increased latency to feed in a novelty-suppressed feeding test.

Behavioral effects of hindbrain vasotocin in goldfish are seasonally variable but not sexually dimorphic.

We have previously demonstrated that centrally administered vasotocin (VT) inhibits social approach toward same-sex conspecifics in male and female goldfish, and that this behavioral effect is dependent upon VT projections to the hindbrain. We now show that there are no sex differences in sensitivity to the behavioral effects of VT, though differences do exist in responsiveness across seasons in both sexes. A central dose of 1 microg, but not 200 ng, inhibited social approach in goldfish in non-reproductive condition, whereas a dose as low as 40 ng inhibited social approach in fish in full reproductive condition.

Olfactory biopsies demonstrate a defect in neuronal development in Rett's syndrome.

Rett's Syndrome (RTT) is a neurodevelopmental disorder resulting from mutation in the mecp2 gene that encodes methyl CpG binding protein 2, a transcriptional repressor. Because this disease primarily affects neurons, tissue is not available during active disease. We used the olfactory system as a model to investigate abnormalities in neuronal development in RTT, because olfactory receptor neurons (ORNs) are replaced throughout life by ongoing postnatal neurogenesis.

Rapid genotyping of common MeCP2 mutations with an electronic DNA microchip using serial differential hybridization.

Rett syndrome is a neurodevelopmental disorder that affects females almost exclusively, and in which eight common point mutations on the X-linked MeCP2 gene are knows to cause over 70% of mutation-positive cases. We explored the use of a novel platform to detect the eight common mutations in Rett syndrome patients to expedite and simplify the process of identification of known genotypes. The Nanogen workstation consists of a two-color assay based on electric hybridization and thermal discrimination, all performed on an electronically active NanoChip.

Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy.

Deficiencies in the activity of cytochrome c oxidase (COX), the terminal enzyme in the respiratory chain, are a frequent cause of autosomal recessive mitochondrial disease in infants. These patients are clinically and genetically heterogeneous, and all defects so far identified in this group have been found in genes coding for accessory proteins that play important roles in the assembly of the COX holoenzyme complex. Many patients, however, remain without a molecular diagnosis.

Associations between MeCP2 mutations, X-chromosome inactivation, and phenotype.

Rett syndrome is a neurodevelopmental disorder of early postnatal brain growth in girls. Patients show a normal neonatal period with subsequent developmental regression and a loss of acquired skills (communication and motor skills), deceleration of head growth, and development of typical hand stereotypies. Recent studies have shown that mutations in the X-linked methyl CpG binding protein 2 gene (MeCP2) cause most typical cases of Rett syndrome.

MeCP2 mutations in children with and without the phenotype of Rett syndrome.

Background: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked methyl CpG binding protein 2 (MeCP2) gene.

Methods: One hundred sixteen patients with classical and atypical RTT were studied for mutations of the MeCP2 gene by using DHPLC and direct sequencing.

Results: Causative mutations in the MeCP2 gene were identified in 63% of patients, representing a total of 30 different mutations.

Social facilitation of object-oriented hand use in a Rett syndrome variant girl: implications for partial preservation of an hypothesized specialized cerebral network.

Partial preservation of object-oriented hand use (OOHU) was studied behaviorally in a 6-1/2-year-old girl with the preserved speech variant (PSV) of Rett syndrome (RS), associated with a T 158 missense MeCP2 mutation and favorably skewed X-inactivation. At home, OOHU was limited except for self-feeding. When examined, overall time invested in toy play was only 38% of that of healthy subjects, and also, by comparison with healthy subjects, less when autonomous than when socially-facilitated (13% vs 63%).

A pathogenic 15-base pair deletion in mitochondrial DNA-encoded cytochrome c oxidase subunit III results in the absence of functional cytochrome c oxidase.

A 15-base pair, in-frame, deletion (9480del15) in the mitochondrial DNA (mtDNA)-encoded cytochrome c oxidase subunit III (COX III) gene was identified previously in a patient with recurrent episodes of myoglobinuria and an isolated COX deficiency. Transmitochondrial cell lines harboring 0, 97, and 100% of the 9480del15 deletion were created by fusing human cells lacking mtDNA (rho(0) cells) with platelet and lymphocyte fractions isolated from the patient. The COX III gene mutation resulted in a severe respiratory chain defect in all mutant cell lines.

A microdeletion in cytochrome c oxidase (COX) subunit III associated with COX deficiency and recurrent myoglobinuria.

We have identified a 15-bp microdeletion in a highly conserved region of the mitochondrially encoded gene for cytochrome c oxidase (COX) subunit III in a patient with severe isolated COX deficiency and recurrent myoglobinuria. The mutant mitochondrial DNA (mtDNA) comprised 92% of the mtDNA in muscle and 0.7% in leukocytes.

Lack of evidence for maternal effect in familial Alzheimer's disease.

Mitochondrial defects may be involved in Alzheimer's disease (AD) by lowering the oxidative phosphorylation efficiency at an earlier age. To investigate the possible contribution of an inherited mitochondrial DNA defect to familial AD (FAD), we examined the Genetic Analysis Workshop (GAW) data for evidence of maternal transmission and the effect on the age of onset. We found no evidence in support of inherited mitochondrial defects in the GAW FAD kindreds.