| RRC ID |
21800
|
| 著者 |
Xu S, Hayashi Y, Takagishi Y, Itoh M, Murata Y.
|
| タイトル |
Aristaless-related homeobox plays a key role in hyperplasia of the pancreas islet α-like cells in mice deficient in proglucagon-derived peptides.
|
| ジャーナル |
PLoS One
|
| Abstract |
Defects in glucagon action can cause hyperplasia of islet α-cells, however, the underlying mechanisms remain largely to be elucidated. Mice homozygous for a glucagon-GFP knock-in allele (Gcg(gfp/gfp) ) completely lack proglucagon-derived peptides and exhibit hyperplasia of GFP-positive α-like cells. Expression of the transcription factor, aristaless-related homeobox (ARX), is also increased in the Gcg(gfp/gfp) pancreas. Here, we sought to elucidate the role of ARX in the hyperplasia of α-like cells through analyses of two Arx mutant alleles (Arx(P355L/Y) and Arx ([330insGCG]7/Y) ) that have different levels of impairment of their function. Expression of Gfp and Arx genes was higher and the size and number of islets increased in the Gcg(gfp/gfp) pancreas compared to and Gcg(gfp/+) pancreas at 2 weeks of age. In male Gcg(gfp/gfp) mice that are hemizygous for the Arx(P355L/Y) mutation that results in a protein with a P355L amino acid substitution, expression of Gfp mRNA in the pancreas was comparable to that in control Gcg(gfp/+)Arx(+/Y) mice. The increases in islet size and number were also reduced in these mice. Immunohistochemical analysis showed that the number of GFP-positive cells was comparable in Gcg(gfp/gfp) Arx(P355L/Y) and Gcg(gfp/+)Arx(+/Y) mice. These results indicate that the hyperplasia is reduced by introduction of an Arx mutation. Arx(P355L/Y) mice appeared to be phenotypically normal; however, Arx ([330insGCG]7/Y) mice that have a mutant ARX protein with expansion of the polyalanine tract had a reduced body size and shortened life span. The number of GFP positive cells was further reduced in the Gcg(gfp/gfp) Arx ([330insGCG]7/Y) mice. Taken together, our findings show that the function of ARX is one of the key modifiers for hyperplasia of islet α-like cells in the absence of proglucagon-derived peptides.
|
| 巻・号 |
8(5)
|
| ページ |
e64415
|
| 公開日 |
2013-1-1
|
| DOI |
10.1371/journal.pone.0064415
|
| PII |
PONE-D-13-05274
|
| PMID |
23671715
|
| PMC |
PMC3650067
|
| MeSH |
Animals
Blood Glucose / metabolism
Body Weight
Female
Gene Expression
Glucagon / genetics
Glucagon / metabolism
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Hyperplasia
Immunohistochemistry
Islets of Langerhans / metabolism*
Islets of Langerhans / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Fluorescence
Mutation
Peptides / genetics
Peptides / metabolism*
Proglucagon / genetics
Proglucagon / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / genetics
Transcription Factors / metabolism*
|
| IF |
2.74
|
| 引用数 |
3
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| 実験動物マウス |
RBRC03654
RBRC03661 |
