PMID- 17652166
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20071023
IS  - 1531-2267 (Electronic)
IS  - 1094-8341 (Linking)
VI  - 31
IP  - 2
DP  - 2007 Oct 22
TI  - Disruption of a novel regulatory locus results in decreased Bdnf expression, 
      obesity, and type 2 diabetes in mice.
PG  - 252-63
AB  - Mutants of brain-derived neurotrophic factor (BDNF) are associated with obesity. 
      However, the regulatory mechanism of BDNF expression is still unclear. We 
      developed a novel mutant mouse line, transgenic insertional mutants with obesity, 
      named Timo, in which a potential regulatory locus of Bdnf was disrupted by 
      transgene insertion. The insertion site was identified and lies 857 kb upstream 
      of the Bdnf gene. The disrupted genomic locus is conserved across the mouse, rat, 
      dog, and human genome and contains several highly conserved elements that are 
      able to upregulate reporter gene expression in vitro. Along with downregulation 
      of BDNF to approximately 30% of wild-type animals, Timo/Timo mice exhibited 
      increased body weight and fat content with hepatic steatosis and elevated serum 
      levels of leptin, cholesterol, and LDL cholesterol. These mutant mice also showed 
      obesity-independent insulin resistance, hyperinsulinemia, impaired glucose 
      tolerance, age-dependent hyperglycemia, and shortened life span. Molecular and 
      phenotype analysis of Timo/Timo mice indicated the existence of a genome locus, 
      lying 857 kb upstream of the Bdnf gene, that regulates BDNF expression, body 
      weight, and glucose homeostasis.
FAU - Sha, Haibo
AU  - Sha H
AD  - Model Animal Research Center, State Key Laboratory of Pharmaceutical 
      Biotechnology, Nanjing University, Nanjing, China.
FAU - Xu, Jingyue
AU  - Xu J
FAU - Tang, Jing
AU  - Tang J
FAU - Ding, Jun
AU  - Ding J
FAU - Gong, Jianfeng
AU  - Gong J
FAU - Ge, Xiaomei
AU  - Ge X
FAU - Kong, Dong
AU  - Kong D
FAU - Gao, Xiang
AU  - Gao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070724
PL  - United States
TA  - Physiol Genomics
JT  - Physiological genomics
JID - 9815683
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*genetics
MH  - Cell Line
MH  - Chromosome Mapping
MH  - Conserved Sequence
MH  - Crosses, Genetic
MH  - Diabetes Mellitus, Type 2/blood/*genetics
MH  - Female
MH  - Genes, Regulator/*genetics
MH  - Genes, Reporter
MH  - Humans
MH  - Hyperphagia/genetics
MH  - Insulin Resistance/genetics
MH  - Liver/metabolism
MH  - Longevity/genetics
MH  - Male
MH  - Mammals/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Mutagenesis, Insertional
MH  - Obesity/blood/*genetics
MH  - Species Specificity
MH  - Transgenes
EDAT- 2007/07/27 09:00
MHDA- 2007/12/14 09:00
CRDT- 2007/07/27 09:00
PHST- 2007/07/27 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/07/27 09:00 [entrez]
AID - 00093.2007 [pii]
AID - 10.1152/physiolgenomics.00093.2007 [doi]
PST - ppublish
SO  - Physiol Genomics. 2007 Oct 22;31(2):252-63. doi: 
      10.1152/physiolgenomics.00093.2007. Epub 2007 Jul 24.