GAP-43 transgenic mice: dispersed genomic sequences confer a GAP-43-like expression pattern during development and regeneration.
Using transgenic mice, we have examined the expression pattern conferred by regions of genomic GAP-43 coupled to beta-galactosidase. We demonstrate that gene constructions that include the GAP-43 5'-flanking region along with sufficient sequences of the first intron drive beta-galactosidase (lacZ) expression to mimic in many regards the complex spatial and temporal pattern of endogenous GAP-43 expression. Transgene expression reaches peak levels during development, and persists at high levels in particular adult brain regions, such as the hippocampus and olfactory bulb. The inclusion of a stretch of the first intron in the construction is necessary to prevent expression outside of the nervous system, indicating that some of the cell specificity of GAP-43 expression is due to suppression of expression in inappropriate tissues. Injury caused by sciatic nerve crush causes reexpression of the transgene in adult sensory and motor neurons. This genomic region of GAP-43, therefore, includes elements responsive to neuronal growth signals that regulate both development and regeneration.
Vanselow
J
J
Developmental Biology Laboratory, Massachusetts General Hospital, Boston.
Grabczyk
E
E
Ping
J
J
Baetscher
M
M
Teng
S
S
Fishman
M C
MC
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000502:physiology; D005314:Embryonic and Fetal Development; D019922:GAP-43 Protein; D006624:Hippocampus / Q000378:metabolism; D007438:Introns; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D016900:Neurofilament Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D009928:Organ Specificity; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D012584:Sciatic Nerve / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*; D001616:beta-Galactosidase / Q000096:biosynthesis
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase