Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Focusing forward genetics: a tripartite ENU screen for neurodevelopmental mutations in the mouse.

Genetics | Jul 11, 2011

The control of growth, patterning, and differentiation of the mammalian forebrain has a large genetic component, and many human disease loci associated with cortical malformations have been identified. To further understand the genes involved in controlling neural development, we have performed a forward genetic screen in the mouse (Mus musculus) using ENU mutagenesis. We report the results from our ENU screen in which we biased our ascertainment toward mutations affecting neurodevelopment. Our screen had three components: a careful morphological and histological examination of forebrain structure, the inclusion of a retinoic acid response element-lacZ reporter transgene to highlight patterning of the brain, and the use of a genetically sensitizing locus, Lis1/Pafah1b1, to predispose animals to neurodevelopmental defects. We recovered and mapped eight monogenic mutations, seven of which affect neurodevelopment. We have evidence for a causal gene in four of the eight mutations. We describe in detail two of these: a mutation in the planar cell polarity gene scribbled homolog (Drosophila) (Scrib) and a mutation in caspase-3 (Casp3). We find that refining ENU mutagenesis in these ways is an efficient experimental approach and that investigation of the developing mammalian nervous system using forward genetic experiments is highly productive.

Pubmed ID: 21515572 RIS Download

Mesh terms: 1-Alkyl-2-acetylglycerophosphocholine Esterase | Animals | Caspase 3 | Chromosome Mapping | Crosses, Genetic | DNA Fingerprinting | Ethylnitrosourea | Female | Gene Expression Regulation, Developmental | Genes, Reporter | Genetic Association Studies | Heterozygote | High-Throughput Screening Assays | Homozygote | Humans | Immunohistochemistry | Intracellular Signaling Peptides and Proteins | Male | Mice | Microtubule-Associated Proteins | Mutagens | Mutation | Nervous System Diseases | Phenotype | Polymorphism, Single Nucleotide | Prosencephalon | Transgenes

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIMH NIH HHS, Id: R01 MH081187
  • Agency: NICHD NIH HHS, Id: F32 HD053198
  • Agency: NIMH NIH HHS, Id: R01MH081187
  • Agency: NICHD NIH HHS, Id: R01HD0306404
  • Agency: NICHD NIH HHS, Id: F32HD053198

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.