PMID- 10915774
OWN - NLM
STAT- MEDLINE
DCOM- 20001027
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 9
IP  - 12
DP  - 2000 Jul 22
TI  - Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene 
      (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 
      mouse models of Down syndrome.
PG  - 1853-64
AB  - The Drosophila single-minded (sim) transcription factor, is a master regulator of 
      fruitfly neurogenesis. Recently, we have cloned and mapped a human homolog of 
      sim, SIM2, to chromosome 21 in the so-called 'Down syndrome chromosomal region'. 
      Three copies of SIM2 may contribute to some Down syndrome (DS) phenotypes because 
      of the mapping position function as transcriptional repressor, temporal and 
      spatial expression pattern of mouse Sim2, and the potentially analogous role of 
      human SIM2 to that of Drosophila sim during neurogenesis. In order to validate 
      this hypothesis in vivo, we have created the first bacterial artificial 
      chromosome transgenic mice overexpressing a gene possibly involved in DS with 
      only one or two additional copies of mouse Sim2. The transgene was shown to be 
      expressed in the same spatial pattern as the endogenous gene. The mice develop 
      normally, are fertile and do not show detectable histopathological abnormalities. 
      However, detailed analysis of their behavior revealed anxiety-related/reduced 
      exploratory behaviour and sensitivity to pain, phenotypes similar to those also 
      present in other partial trisomy 16 mouse models of DS. Our data therefore 
      suggest that overexpression of SIM2 contributes to some of the complex DS 
      phenotypes.
FAU - Chrast, R
AU  - Chrast R
AD  - Division of Medical Genetics, Geneva University Medical School and University 
      Hospital, 1 Rue Michel-Servet, CH-1211 Geneve 4, Switzerland.
FAU - Scott, H S
AU  - Scott HS
FAU - Madani, R
AU  - Madani R
FAU - Huber, L
AU  - Huber L
FAU - Wolfer, D P
AU  - Wolfer DP
FAU - Prinz, M
AU  - Prinz M
FAU - Aguzzi, A
AU  - Aguzzi A
FAU - Lipp, H P
AU  - Lipp HP
FAU - Antonarakis, S E
AU  - Antonarakis SE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (SIM2 protein, human)
RN  - 0 (sim protein, Drosophila)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - Behavior, Animal
MH  - Chromosomes, Bacterial
MH  - DNA-Binding Proteins/genetics/*physiology
MH  - Disease Models, Animal
MH  - Down Syndrome/*etiology
MH  - Drosophila Proteins
MH  - Female
MH  - Gene Dosage
MH  - Gene Expression Profiling
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Motor Activity
MH  - Nuclear Proteins/genetics/*physiology
MH  - Pain Measurement
MH  - Phenotype
MH  - Social Behavior
MH  - Stress, Physiological
MH  - Trisomy
EDAT- 2000/08/01 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/01 11:00
PHST- 2000/08/01 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/01 11:00 [entrez]
AID - 10.1093/hmg/9.12.1853 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2000 Jul 22;9(12):1853-64. doi: 10.1093/hmg/9.12.1853.