The human neuregulin-2 (NRG2) gene: cloning, mapping and evaluation as a candidate for the autosomal recessive form of Charcot-Marie-Tooth disease linked to 5q

  title={The human neuregulin-2 (NRG2) gene: cloning, mapping and evaluation as a candidate for the autosomal recessive form of Charcot-Marie-Tooth disease linked to 5q},
  author={Huijun Z. Ring and H Chang and Ang{\`e}le Guilbot and Alexis Brice and Eric Leguern and Uta Francke},
  journal={Human Genetics},
Neuregulin-2 (NRG2) is a novel member of the neuregulin family of growth and differentiation factors. Through interaction with the ErbB family of receptors, neuregulin-2 induces the growth and differentiation of epithelial, neuronal, glial and other types of cells. In this study, we have cloned the human neuregulin-2 gene, and determined its genomic structure and alternative splicing patterns. By using radiation hybrid mapping panels, the human NRG2 gene was mapped to the D5S658–D5S402 region… 

Fine mapping of new glaucoma locus GLC1M and exclusion of neuregulin 2 as the causative gene

The critical interval of GLC1M was refined to a region of 28 Mb between D5S2051 and NRG2, and theNRG2 gene was excluded as the causative gene for JOAG.

Generation and Characterization of Neuregulin-2-Deficient Mice

It is indicated that in vivoNRG-2 activity differs substantially from that of NRG-1 and that it is not essential for normal development in utero.

Multiple personalities of neuregulin gene family members

These latest findings tantalize us with the notion that the sibling members of this gene family are playing quite different, perhaps complementary, functional roles in establishing CNS synapses.

The Neuregulin Family of Genes and their Multiple Splice Variants in Breast Cancer

All four neuregulin genes are expressed and play an important role in mammary gland development and their presence may affect the efficacy of treatment with endocrine agents or with signal transduction inhibitors directed at the EGF receptor family members.

Neuregulins 1–4 are expressed in the cytoplasm or nuclei of ductal carcinoma (in situ) of the human breast

Each member of the NRG family of ligands is present in pre-invasive ductal breast cancer and that they may be involved in regulating cell behaviour, suggesting a novel mechanism of action for some of these proteins.

The Molecular Function of PURA and Its Implications in Neurological Diseases

This review aims to provide a comprehensive assessment of research of the last 30 years on PURA and its recently discovered involvement in neuropathological abnormalities, informing researchers as well as clinicians on the current knowledge of PURA’s molecular and cellular functions aswell as its implications in very different neuronal disorders.

The Role of Neuregulin 1 β /ErbB signaling in the heart

Insight is provided as to why ErbB2-targeted cancer treatments have deleterious effects on cardiac function in some cancer patients and emerging data suggest that Nrg-1 ligands might be useful clinically to restore cardiac function after cardiac injury.



Ligands for ErbB-family receptors encoded by a neuregulin-like gene

Northern blot and in situ hybridization analysis of adult rat tissues indicate that expression of neurgulin-2 is highest in the cerebellum, and the expression pattern is different from that of neuregulins.

Characterization of a neuregulin-related gene, Don-1, that is highly expressed in restricted regions of the cerebellum and hippocampus

The cloning and initial characterization of a second ligand for the erbB family of receptors is reported here on, which is termed Don-1 (divergent of neuregulin 1), and has structural similarity with the neurgulins.

A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4.

A novel member of the epidermal growth factor (EGF) family, the neural- and thymus-derived activator for ErbB kinases (NTAK), has been purified and cloned and appears to be a new members of the EGF family displaying neuregulin properties.

Isoform-specific expression and function of neuregulin.

It is shown here that targeted mutations that affect different isoforms result in distinct phenotypes, demonstrating that isoforms can take over specific functions in vivo.

Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases

The results indicate that NRG-1 andNRG-2 mediate distinct biological processes by acting at different sites in tissues and eliciting different biochemical responses in cells.

Homozygosity Mapping of an Autosomal Recessive Form of Demyelinating Charcot-Marie-Tooth Disease to Chromosome 5q23–q33

By homozygosity mapping in a large Algerian kindred, a second locus for autosomal recessive CMT is assigned to chromosome 5q23-33.1 by linkage analysis demonstrated that the same locus is involved in a second Algerian family with a demyelinating CMT.

The influence of heregulins on human Schwann cell proliferation

It is demonstrated that HRG is an effective mitogen for human SCs and that, in the presence of agents that elevate cAMP, it is possible to expand these cells over multiple passages without overwhelming fibroblast contamination.

A clinical, electrophysiologic, neuropathologic, and genetic study of two large Algerian families with an autosomal recessive demyelinating form of Charcot‐Marie‐Tooth disease

Two large consanguineous Algerian families with an autosomal recessive demyelinating CMT and similar clinical manifestations are reported, suggesting a subtype of autosomic recessive neuropathy, the locus of which is undetermined.

Severe neuropathies in mice with targeted mutations in the ErbB3 receptor

It is shown that sensory and motor neurons require factors for their survival that are provided by developing Schwann cells, and that ErbB3 functions in a cell-autonomous way during the development of SchwANN cells, but not in the survival of sensory or motor neurons.

Embryonic Development of Schwann Cells: Multiple Roles for Neuregulins along the Pathway

These studies point in particular to major roles for neuregulins which appear to be involved in the control of cell survival, proliferation, and differentiation, as well as of gene expression at different levels of the pathway.