- 作者: Gerard Honig; Angela Liou; Miles Berger; Michael S German; Laurence H Tecott
- 作者服務機構: Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA, USA
- 中文摘要: --
- 英文摘要:
Background: Multicellular organisms are characterized by a remarkable diversity of
morphologically distinct and functionally specialized cell types. Transgenic
techniques for the manipulation of gene expression in specific cellular populations
are highly useful for elucidating the development and function of these cellular
populations. Given notable similarities in developmental gene expression between
pancreatic β-cells and serotonergic neurons, we examined the pattern of Cremediated
recombination in the nervous system of a widely used mouse line, Pdx1-
cre (formal designation, Tg(Ipf1-cre)89.1Dam), in which the expression of Cre
recombinase is driven by regulatory elements upstream of the pdx1 (pancreaticduodenal
homeobox 1) gene.
Methods: Single (hemizygous) transgenic mice of the pdx1-creCre/0 genotype were bred to
single (hemizygous) transgenic reporter mice (Z/EG and rosa26R lines).
Recombination pattern was examined in offspring using whole-mount and sectioned
histological preparations at e9.5, e10.5, e11.5, e16.5 and adult developmental
stages. Results : In addition to the previously reported pancreatic recombination, recombination in the
developing nervous system and inner ear formation was observed. In the central
nervous system, we observed a highly specific pattern of recombination in neuronal
progenitors in the ventral brainstem and diencephalon. In the rostral brainstem (r1-
r2), recombination occurred in newborn serotonergic neurons. In the caudal
brainstem, recombination occurred in non-serotonergic cells. In the adult, this
resulted in reporter expression in the vast majority of forebrain-projecting
serotonergic neurons (located in the dorsal and median raphe nuclei) but in none of
the spinal cord-projecting serotonergic neurons of the caudal raphe nuclei. In the
adult caudal brainstem, reporter expression was widespread in the inferior olive
nucleus. In the adult hypothalamus, recombination was observed in the arcuate
nucleus and dorsomedial hypothalamus. Recombination was not observed in any
other region of the central nervous system. Neuronal expression of endogenous
pdx1 was not observed. Conclusions : The Pdx1-cre mouse line, and the regulatory elements contained in the
corresponding transgene, could be a valuable tool for targeted genetic manipulation
of developing forebrain-projecting serotonergic neurons and several other unique
neuronal sub-populations. These results suggest that investigators employing this
mouse line for studies of pancreatic function should consider the possible
contributions of central nervous system effects towards resulting phenotypes. - 中文關鍵字: --
- 英文關鍵字: --