Cre/loxP-mediated inactivation of the bHLH transcription factor gene NeuroD/BETA2

Genesis. 2005 Aug;42(4):247-52. doi: 10.1002/gene.20138.

Abstract

NeuroD/Beta2 is a basic helix-loop-helix (bHLH) transcription factor with important functions during development of the pancreas and the nervous system. NeuroD null mutant mice die perinatally due to diabetes caused by impaired differentiation of pancreatic endocrine cells. Additionally, null mutants display severe defects in the formation of cerebellar and hippocampal granule cells, inner ear sensory neurons, and retinal photoreceptor cells. For spatio-temporally restricted inactivation of the NeuroD gene, we generated conditional mouse mutants by flanking the NeuroD coding region with loxP sites. Homozygous NeuroD(loxP) mutant mice are fully viable and express normal levels of NeuroD mRNA and protein. Breeding NeuroD(loxP) mice to Tg(malpha6-Cre)B1LFR mice that express Cre recombinase under control of the GABA(A) receptor alpha6 subunit promoter resulted in efficient inactivation of the NeuroD gene in post-migratory cerebellar granule cells and a subset of brainstem nuclei. The NeuroD(loxP) mouse mutant will be a valuable tool to study the developmental and adult function of NeuroD in nervous system and pancreas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Technical Report

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation / genetics
  • Central Nervous System / cytology
  • Central Nervous System / growth & development
  • DNA-Binding Proteins / genetics*
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics
  • Gene Expression Regulation, Developmental*
  • Gene Transfer Techniques
  • Genotype
  • Helix-Loop-Helix Motifs / genetics*
  • Immunohistochemistry
  • Integrases / biosynthesis
  • Integrases / genetics
  • Mice
  • Mice, Neurologic Mutants / genetics*
  • Models, Animal
  • Nerve Tissue Proteins / genetics*
  • Pancreas / cytology
  • Pancreas / growth & development
  • Protein-Lysine 6-Oxidase / biosynthesis
  • Protein-Lysine 6-Oxidase / genetics
  • Trans-Activators / genetics*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Neurod1 protein, mouse
  • Trans-Activators
  • Lox protein, mouse
  • NeuroD protein
  • Protein-Lysine 6-Oxidase
  • Cre recombinase
  • Integrases