SIM2

Single-minded homolog 2 is a is_associated_with::protein that in humans is encoded by the SIM2 is_associated_with::gene. It plays a mojor role in the development of the is_associated_with::CNS midline as well as the construction of the face and head.

Function
is_associated_with::SIM1 and SIM2 genes are is_associated_with::Drosophila single-minded (sim) gene homologs. The Drosophila sim gene encodes a is_associated_with::transcription factor that is a master regulator of is_associated_with::neurogenesis of midline cells in the central nervous system. SIM2 maps within the so-called is_associated_with::Down syndrome chromosomal region, specifically on the is_associated_with::q arm of is_associated_with::chromosome 21, band 22.2. Based on the mapping position, its potential function as transcriptional repressor and similarity to Drosophila sim, it is proposed that SIM2 may contribute to some specific Down syndrome phenotypes

Interactions
SIM2 has been shown to interact with is_associated_with::Aryl hydrocarbon receptor nuclear translocator.

When the SIM2 gene is tranfected into is_associated_with::PC12 cells, it effects the normal cycle of cell maturation. SIM2 inhibits the expression of is_associated_with::cyclin E, which in turn inhibits the cell's ability to pass through the is_associated_with::G1/S checkpoint and suppresses the cell's proliferation ability. it also up-regulates the presence of is_associated_with::p27, a growth is_associated_with::inhibitor protein. The presence of p27 inhibits the activation of cell cycle regulatory is_associated_with::kinases.

Disease State
There are three states of the gene: +/+, +/-, and -/-. When the gene is expressed as SIM2 -/-, it is considered disrupted and many physical malformations are seen, particularly in the is_associated_with::craniofacial area. Individuals with SIM2 -/- have either a full or partial is_associated_with::secondary palate is_associated_with::cleft and malformations in the tongue and is_associated_with::pterygoid processes of the sphenoid bone. These malformations cause is_associated_with::aerophagia, or the swallowing of air, and is_associated_with::postnatal death. Severe aerophagia leads to accumulation of air in the is_associated_with::gastrointestinal tract, causing the belly to be distended.

It is thought that the over-expression of the SIM2 gene brings about some of the phenotypic deformities that are characteristic of is_associated_with::Down syndrome. The presence of SIM2 is_associated_with::mRNA in many parts of the brain known to show deformities in individuals with Down syndrome, as well as in the is_associated_with::palate, oral and tongue is_associated_with::epithelia, is_associated_with::mandibular and is_associated_with::hyoid bones.

Knockout Model
Scientists can purposefully "knockout" or cause the gene to be disrupted. To do this, they perform is_associated_with::homologous recombination and eliminate the predicted start codon and the following 47 is_associated_with::amino acids. Then the is_associated_with::EcoRI restriction site is introduced into the chromosome.