Wocko, a neurological mutant generated in a transgenic mouse pedigree

• Published in: The Journal of neuroscience 1991-06, Vol.11 (6), p.1524-1530
• Main Authors: Crenshaw, EB, 3d, Ryan, A, Dillon, SR, Kalla, K, Rosenfeld, MG
• Format: Article
• Language: English
• Subjects: Animals; Avian Sarcoma Viruses - genetics; Base Sequence; Biological and medical sciences; Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation; Female; Fundamental and applied biological sciences. Psychology; Genes, src; Humans; Male; Mice; Mice, Neurologic Mutants - genetics; Mice, Transgenic - genetics; Molecular Sequence Data; Oligonucleotide Probes; Phenotype; Polymerase Chain Reaction; Promoter Regions, Genetic; RNA, Messenger - analysis; RNA, Messenger - genetics; Vasopressins - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.11-06-01524.1991

Naturally occurring mutations involving the nervous system have provided virtually all of our current understanding of the genetic regulation of neural development (Caviness and Rakic, 1978). The difficulty of isolating the corresponding genes, however, has precluded a molecular analysis of these mutants. Insertional mutagenesis, induced by microinjection of DNA into fertilized ova to produce transgenic animals, provides a molecular tag that marks the site of the mutational event. In this article, we describe a transgenic neurological mutation, designated wocko (Wo), which disrupts the development of the inner ear. These mutant mice display a dominant behavioral phenotype that consists of circling, hyperactivity, and head tossing, reminiscent of the shaker/waltzer class of mutants, and they display a recessive homozygous sublethal phenotype. Anatomical analyses showed that both structural and neural components of the vestibular system were disrupted, while analyses of mutant fetuses showed that these morphological abnormalities were due to aberrant development. Although low levels of transgene expression were detected using a sensitive PCR assay, several nonmutant pedigrees that contain the same construct also expressed the transgene in the inner ear, suggesting that low levels of transgene expression alone were not responsible for the wocko phenotype. Because the integrated transgene provides a marker to clone the wocko mutation, the analysis of this mutant will give unique insight into the molecular genetics of inner ear development and into a broad class of neurological mutations that affect the inner ear.