Pbx1 and Meis1 regulate activity of the Xenopus laevis Zic3 promoter through a highly conserved region.

Xenopus Zic3 (zinc finger in the cerebellum-3) is expressed in the dorsal neural tube of tailbud embryos and tadpoles. We have isolated a 3.1kb DNA fragment from the Xenopus laevis Zic3 locus that drives proper expression of a GFP reporter in transgenic frog tailbud embryos and tadpoles.

Xenopus laevis FoxE1 is primarily expressed in the developing pituitary and thyroid.

The members of the FoxE subfamily of Fox (forkhead) genes are expressed in the developing pituitary, thyroid and lens. Mammalian Foxe1 is expressed primarily in the developing pituitary and thyroid gland, Foxe3 is expressed in the developing lens, while Xenopus FoxE4 is expressed in the developing lens and thyroid. Here we report the identification of Xenopus FoxE1, a gene that is primarily expressed in the developing pituitary and thyroid.

Expression of a novel Ski-like gene in Xenopus development.

Members of the Ski/Sno family of gene products contain a characteristic peptide domain involved in protein-protein or protein-DNA interaction. Here, we characterize the developmental expression of xDawg, in Xenopus laevis, of a new gene, related to the Ski/Sno family of transcription regulators. The Ski/Sno domain of xDawg is predicted to present an electropositive surface, consistent with a role in DNA binding.

Changes in gene expression associated with loss of function of the NSDHL sterol dehydrogenase in mouse embryonic fibroblasts.

Seven human disorders of postsqualene cholesterol biosynthesis have been described. One of these, congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome, results from mutations in the X-linked gene NADH sterol dehydrogenase-like (NSDHL) encoding a sterol dehydrogenase. A series of mutant alleles of the murine Nsdhl gene are carried by bare patches (Bpa) mice, with Bpa(1H) representing a null allele.

Recombineered Xenopus tropicalis BAC expresses a GFP reporter under the control of Arx transcriptional regulatory elements in transgenic Xenopus laevis embryos.

The aristaless-related homeobox (Arx) gene is expressed in a dynamic pattern in the developing vertebrate forebrain. We identified a bacterial artificial chromosome (BAC) containing the Xenopus tropicalis Arx gene and replaced a portion of the first coding exon with a green fluorescent protein (GFP) expression cassette by homologous recombination in bacteria (recombineering). Transgenic X.

Placental defects are associated with male lethality in bare patches and striated embryos deficient in the NAD(P)H Steroid Dehydrogenase-like (NSDHL) Enzyme.

NSDHL is a 3beta-hydroxysterol dehydrogenase that is involved in the removal of C-4 methyl groups in one of the later steps of cholesterol biosynthesis. Mutations in the Nsdhl gene are associated with the X-linked male lethal mouse mutations bare patches (Bpa) and striated (Str), as well as with most cases of human CHILD syndrome. To begin to examine the pathogenesis of these disorders, we have determined that affected male embryos for several Nsdhl alleles die in midgestation, between E10.

Xenopus aristaless-related homeobox (xARX) gene product functions as both a transcriptional activator and repressor in forebrain development.

Mutations in the aristaless-related homeobox (ARX) gene have been found in patients with a variety of X-linked mental retardation syndromes with forebrain abnormalities, including lissencephaly. Arx is expressed in the developing mouse, Xenopus, and zebrafish forebrain. We have used whole-mount in situ hybridization, overexpression, and loss-of-function studies to investigate the involvement of xArx in Xenopus brain development.

Complete complement components C4A and C4B deficiencies in human kidney diseases and systemic lupus erythematosus.

Although a heterozygous deficiency of either complement component C4A or C4B is common, and each has a frequency of approximately 20% in a Caucasian population, complete deficiencies of both C4A and C4B proteins are extremely rare. In this paper the clinical courses for seven complete C4 deficiency patients are described in detail, and the molecular defects for complete C4 deficiencies are elucidated. Three patients with homozygous HLA A24 Cw7 B38 DR13 had systemic lupus erythematosus, mesangial glomerulonephritis, and severe skin lesions or membranous nephropathy.

Insertion of a Pax6 consensus binding site into the alphaA-crystallin promoter acts as a lens epithelial cell enhancer in transgenic mice.

Purpose: Although the murine alphaA-crystallin promoter is the most commonly used promoter for achieving transgene expression in the developing lens, this promoter directs transgene expression efficiently only in lens fiber cells. The purpose of the present study was to generate promoters capable of directing transgene expression to the entire lens but not to the corneal epithelium.

Methods: Transgenic mice were generated with fragments of the murine alphaA- and alphaB-crystallin promoters, as well as with an alphaA-crystallin promoter engineered with the insertion of a Pax6 consensus binding site driving either human growth hormone (hGH) or Cre recombinase genes.

The intricate role of complement component C4 in human systemic lupus erythematosus.

It was observed about 50 years ago that low serum complement activity or low protein concentrations of complement C4 concurred with disease activities of systemic lupus erythematosus (SLE). Complete deficiencies of complement components C4A and C4B, albeit rare in human populations, are among the strongest genetic risk factors for SLE or lupus-like disease, across HLA haplotypes and racial backgrounds. However, whether heterozygous or partial deficiency of C4A (C4AQ0) or C4B (C4BQ0) is a predisposing factor for SLE has been a highly controversial topic.

Impaired antigen receptor induced calcium mobilization in a phospholipase C-gamma1 deficient B cell line.

B lymphocytes express phospholipase C-gamma(1) (PLC-gamma(1)) and phospholipase C-gamma(2) (PLC-gamma(2)) isozymes. However, the relative importance of these two isozymes in B cell signaling is not known. We report here the identification and analysis of a B cell line deficient in PLC-gamma(1).

Dancing with complement C4 and the RP-C4-CYP21-TNX (RCCX) modules of the major histocompatibility complex.

The number of the complement component C4 genes varies from 2 to 8 in a diploid genome among different human individuals. Three quarters of the C4 genes in Caucasian populations have the endogenous retrovirus, HERV-K(C4), in the ninth intron. The remainder does not.

Identification of two novel mutations in the murine Nsdhl sterol dehydrogenase gene and development of a functional complementation assay in yeast.

Nsdhl is a 3beta-hydroxysterol dehydrogenase that is involved in the removal of C-4 methyl groups in the cholesterol biosynthetic pathway. Mutations in this gene are associated with the X-linked male lethal mouse mutations bare patches (Bpa) and striated (Str) and human CHILD syndrome. We have now detected the missense mutations V53D and A94T in conserved amino acids in two additional Bpa alleles.

NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets.

NSDHL, for NAD(P)H steroid dehydrogenase-like, encodes a sterol dehydrogenase or decarboxylase involved in the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis. Mutations in this gene are associated with human CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects), an X-linked, male lethal disorder, as well as the mouse mutations bare patches and striated. In the present study, we have investigated the subcellular localization of tagged proteins encoded by wild-type and selected mutant murine Nsdhl alleles using confocal microscopy.

Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index.

Among the genes and proteins of the human immune system, complement component C4 is extraordinary in its frequent germline variation in the size and number of genes. Definitive genotypic and phenotypic analyses were performed on a central European population to determine the C4 polygenic and gene size variations and their relationships with serum C4A and C4B protein concentrations and hemolytic activities. In a study population of 128 healthy subjects, the number of C4 genes present in a diploid genome varied between two to five, and 77.

The role of ZIC3 in vertebrate development.

ZIC3 is a C2H2 zinc finger transcription factor that is involved in early patterning of the vertebrate embryo. Human patients with mutations in the X-linked ZIC3 gene have a complex developmental phenotype that includes laterality defects, congenital heart disease, and lumbosacral and anal anomalies, including neural tube defects. Similar phenotypes are found in the bent tail (BN) mouse, a spontaneous mutation that is associated with a submicroscopic deletion of the ZIC3 locus, as well as in a ZIC3 null allele generated through homologous recombination.

Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes.

Since 1998, five disorders involving enzyme defects in post-squalene cholesterol biosynthesis have been identified-desmosterolosis, X-linked dominant chondrodysplasia punctata, CHILD syndrome, lathosterolosis, and hydrops-ectopic calcification-moth-eaten skeletal dysplasia. They join the most common cholesterol biosynthetic disorder, Smith-Lemli-Opitz syndrome, whose underlying defect was identified in 1993. All are associated with major developmental malformations that are unusual for metabolic disorders.

The Xenopus arx gene is expressed in the developing rostral forebrain.

The human aristaless-related homeobox ( ARX) gene is mutated in several patients with X-linked mental retardation and/or other neurologic pathologies. We report the isolation and expression pattern of a Xenopus arx gene. Similar to other vertebrate arx genes, Xenopus arx is expressed in the developing telencephalon, diencephalon, and floor plate.

Genomics and hearing impairment.

Hearing impairment is clinically and genetically heterogeneous. There are >400 disorders in which hearing impairment is a characteristic of the syndrome, and family studies demonstrate that there are at least 30 autosomal loci for nonsyndromic hearing impairment. The genes that have been identified encode diaphanous (HDIA1), alpha-tectorin (TECTA), the transcription factor POU4F3, connexin 26 (GJB2), and two unconventional myosins (MYO7A and MYO15), and four novel proteins (PDS, COCH, DFNA5, DFNB9).

An algorithm to approximate the likelihood for pedigree data with loops by cutting.

This paper presents a recursive algorithm to approximate the likelihood in arbitrary pedigrees with loops. The algorithm handles any number and nesting levels of loops in pedigrees. The loops are cut as described in a previous publication and the approximate likelihood is simultaneously computed using the cut pedigree.

Trisomy 8 in alveolar soft part sarcoma.

Cytogenetic studies were performed on an alveolar soft part sarcoma of a 6-year-old boy. An extra chromosome 8 was present in 26 of 28 metaphases analyzed.