Restriction of retinoic acid activity by Cyp26b1 is required for proper timing and patterning of osteogenesis during zebrafish development.

Skeletal syndromes are among the most common birth defects. Vertebrate skeletogenesis involves two major cell types: cartilage-forming chondrocytes and bone-forming osteoblasts. In vitro, both are under the control of retinoic acid (RA), but its exact in vivo effects remained elusive.

The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity.

The Trithorax group (TrxG) is composed of diverse, evolutionary conserved proteins that form chromatin-associated complexes accounting for epigenetic transcriptional memory. However, the molecular mechanisms by which particular loci are marked for reactivation after mitosis are only partially understood. Here, based on genetic analyses in zebrafish, we identify the multidomain protein Brpf1 as a novel TrxG member with a central role during development.

REREa/Atrophin-2 interacts with histone deacetylase and Fgf8 signaling to regulate multiple processes of zebrafish development.

The transcriptional regulator RERE/Atrophin-2 (RERE) is required for the normal patterning of the early vertebrate embryo, including the central nervous system, pharyngeal arches, and limbs. Consistent with a role as a transcriptional corepressor, RERE binds histone deacetylase 1 and 2 (HDAC1/2), and orphan nuclear receptors such as Tlx. Here, we identify the zebrafish babyface (bab) as a mutant in rerea and show that it interacts genetically with fibroblast growth factor 8 (fgf8).

p53 deficiency rescues apoptosis and differentiation of multiple cell types in zebrafish flathead mutants deficient for zygotic DNA polymerase delta1.

Cell culture work has identified the tumor suppressor p53 as a component of the S-phase checkpoint control system, while in vivo studies of this role of p53 in whole-vertebrate systems were limited. Here, we describe zebrafish mutants in the DNA polymerase delta catalytic subunit 1, based on the positional cloning of the flathead (fla) gene. fla mutants display specific defects in late proliferative zones, such as eyes, brain and cartilaginous elements of the visceral head skeleton, where cells display compromised DNA replication, followed by apoptosis, and partial or complete loss of affected tissues.

Defective potassium channel Kir2.1 trafficking underlies Andersen-Tawil syndrome.

Andersen-Tawil syndrome is a skeletal and cardiac muscle disease with developmental features caused by mutations in the inward rectifier K+ channel gene KCNJ2. Patients harboring these mutations exhibit extremely variable expressivities. To explore whether these mutations can be correlated with a specific patient phenotype, we expressed both wild-type (WT) and mutant genes cloned into a bi-cistronic vector.

Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome).

Andersen syndrome (AS) is a rare, inherited disorder characterized by periodic paralysis, long QT (LQT) with ventricular arrhythmias, and skeletal developmental abnormalities. We recently established that AS is caused by mutations in KCNJ2, which encodes the inward rectifier K(+) channel Kir2.1.

Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.

Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family.

Genetic localization of an autosomal dominant leukodystrophy mimicking chronic progressive multiple sclerosis to chromosome 5q31.

The hereditary leukodystrophies represent a group of neurological disorders, in which complete or partial dysmyelination occurs in either the central nervous system (CNS) and/or the peripheral nervous system. Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive, neurological disorder characterized by symmetrical widespread myelin loss in the CNS, and the phenotype is similar to that of chronic progressive multiple sclerosis. We report clinical, neuroradiological and neuropathological data from the originally reported ADLD family.

Genetic localization of the familial adult myoclonic epilepsy (FAME) gene to chromosome 8q24.

Objective: To identify the genetic locus for the familial adult myoclonic epilepsy (FAME) gene.

Background: Idiopathic generalized epilepsy (IGE) represents a collection of disorders in which affected individuals present with recurring seizures that have diffuse onset on EEG. These individuals have no known structural cerebral lesions or other identifiable etiology.

A taste of our quality.

High Point Regional Hospital Laboratory was awarded special recognition in the areas of customer service and human resources for the 1992 CLMA Quality Management Award. This article describes several programs and helpful hints in an effort to share information with other laboratories. These programs and strategies worked for us.