Histological study in the brain of the reelin/Dab1-compound mutant mouse.
The Reelin (Reln)-deficient mouse (reeler) and the Dab1-deficient mouse (yotari) are autosomal recessive mutant mice characterized by cerebellar ataxia. Previously, we reported that Reelin and Dab1 proteins have slightly different functions during the development of the cerebral cortex. To analyze the functional roles of Reelin and Dab1 proteins in detail, we attempted to generate a reelin/Dab1 compound-mutant mouse by breeding heterozygote reeler and yotari mice. We examined the cytoarchitecture of the cerebral and cerebellar cortices and the hippocampus of wild-type (Reln ( +/+ ); Dab1 ( +/+ )), double-heterozygote (Reln ( rl/+ ); Dab1 ( yot/+ )), reeler (Reln ( rl/rl ); Dab1 ( +/+ ), Reln ( rl/rl ); Dab1 ( yot/+ )), yotari (Reln ( +/+ ); Dab1 ( yot/yot ), Reln ( rl/+ ); Dab1 ( yot/yot )), and double-compound-deficient (Reln ( rl/rl ); Dab1 ( yot/yot )) mice. Nissl staining demonstrated that no abnormality was recognized in the mice of reelin/Dab1 double-heterozygote (Reln ( rl/+ ); Dab1 ( yot/+ )). The reelin/Dab1-compound mutant mouse (Reln ( rl/rl ); Dab1 ( yot/yot )) showed histological abnormalities in the cerebral and cerebellar cortices and the hippocampus, in addition to those of reeler and yotari mice. We injected HRP into the lumbar cord of these animals with various gene compositions to examine the distribution pattern of corticospinal tract (CST) neurons. CST neurons of the reelin/Dab1-compound mutant mice were not confined to layer V, but scattered throughout the motor cortex. This quantitative and statistical analysis shows that the distribution pattern of CST neurons of the reelin/Dab1-compound mutant mouse differs from those of either of the reeler or yotari counterparts. Taken together, although Reelin/Dab1 signal transduction is a primary cascade in neurons during developmental periods, other signaling cascades (e.g., the Cdk-5/Dab1 pathway) may lie in a parallel fashion to Reelin/Dab1 signal transduction.
Yamamoto
Tatsuro
T
Division of Developmental Neurobiology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, 650-0017, Japan. tyama@nayoro.ac.jp
Setsu
Tomiyoshi
T
Okuyama-Yamamoto
Ayako
A
Terashima
Toshio
T
D000818:Animals; D001921:Brain / Q000002:abnormalities*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006579:Heterozygote; D006735:Horseradish Peroxidase; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D056347:Neuroanatomical Tract-Tracing Techniques; D011712:Pyramidal Tracts / Q000002:abnormalities*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D015398:Signal Transduction
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D006735:Horseradish Peroxidase; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases