title: Impaired motor coordination in mice that lack punc.
abstract: The punc gene, encoding a member of the neural cell adhesion molecule family expressed in the developing central nervous system, limbs, and inner ear, was identified. To extend studies of the normal expression pattern of punc and to determine its function, a mouse strain bearing a lacZ/neo insertion in a 5' coding exon was created. The complex pattern of punc expression in embryos from embryonic day 9.5 (E9.5) to E11.5 was mimicked accurately by beta-galactosidase (beta-Gal) activity. As development proceeded, the distribution of beta-Gal activity was increasingly restricted, finally becoming confined to the brain and inner ear by E15.5. In the adult, beta-Gal activity was detected in several regions of the inner ear and brain and was particularly strong in the cerebellar Bergmann glia. Genetic analysis of this null allele demonstrated that punc is not required for normal embryogenesis. Interestingly, comparisons of beta-Gal activity and punc transcripts in heterozygous and homozygous mutant individuals demonstrated that punc is negatively autoregulated in some tissues. Adult punc-deficient mice were overtly normal and had normal hearing. Compared with control littermates, however, homozygous mutants had significantly reduced retention times on the Rotarod, suggesting a role for Bergmann glia-expressed Punc in the cerebellar control of motor coordination.
authors.affiliation: Department of Human Genetics, University of Utah, 15 N 2030 E, Salt Lake City, UT 84112, USA.
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: S L
authors.initials: SL
authors.lastname: Mansour
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002874:Chromosome Mapping; D018076:DNA, Complementary; D015536:Down-Regulation; D016057:Evoked Potentials, Auditory, Brain Stem; D005298:Fertility; D015870:Gene Expression; D018390:Gene Targeting; D006706:Homeostasis; D007136:Immunoglobulins / Q000235:genetics / Q000502:physiology*; D007763:Lac Operon; D051379:Mice; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology*; D016254:Mutagenesis, Insertional; D012333:RNA, Messenger; D013550:Swimming
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018076:DNA, Complementary; D007136:Immunoglobulins; C112440:Punc protein, mouse; D012333:RNA, Messenger