In paper citation (Haydar and Reeves, 2011).
I am currently working on my third rotation at Boston University studying the effects of down syndrome (DS) on cortical development in mice. As I looked more intently into DS, I learned a lot about the disorder. Here are my notes from a very relevant overview article that my advisor wrote just last year.
Trisomy 21 is a triplication of human chromosome 21 that causes Down Syndrome. Surprisingly, EVERY child with down syndrome develops Alzheimer's disease later in life. DS also increases the risk of childhood leukemia and causes abnormalities in cardiac and gastrointestinal formation. The average IQ of DS children is around 50. I would like to study why the gene triplication causes intellectual disability.
Mice are not humans, but they do have a mammalian genotype. The homologous region of human chromosome 21 in the mouse is mmu16. I am currently working with a mouse model that has the majority of mmu16 triplicated, Ts65Dn. This mouse model was developed in the early 90's. There are other models, including ones with less of mmu16 triplicated, and one that carries the actual human chromosome 21.
Studying this mouse model is not the same as studying humans with down syndrome, but it does give us a means to examine the development of the brain under similar conditions.
Mouse models of DS have revealed that less excitatory neurons develop in the forebrain of trisomic mammals, and that these neuron differentiate later in development. They also form less excitatory synapses and have more dendritic spine abnormalities. DS model mice also have more PARV and SOM positive cells from the Medial ganglion eminence. This basically indicates an overproduction of inhibitory neurons in the forebrain. One reason for the overproduction of inhibitory neurons might be that Olig1 and Olig 2 are not specifying MGE precursors into oligodendrocytes, thus leaving them to become inhibitory interneurons.
Myelination tends to occur later in the DS model mice, and the cerebellum of DS model mice is smaller with fewer purkinje neurons and only 2/3 of the normal number of granule cells.
One of the major challenges of studying the development of DS model mice is that triplication of various genes does not just affect the expression of those genes, but that it then affects the expression of euploid genes as well. Thus some phenotypes do not arise the same way in cultured cells.
More details to come on individual genes and transcription factors that may be relevant to the DS phenotype in the DS model mice.
I am currently working on my third rotation at Boston University studying the effects of down syndrome (DS) on cortical development in mice. As I looked more intently into DS, I learned a lot about the disorder. Here are my notes from a very relevant overview article that my advisor wrote just last year.
Trisomy 21 is a triplication of human chromosome 21 that causes Down Syndrome. Surprisingly, EVERY child with down syndrome develops Alzheimer's disease later in life. DS also increases the risk of childhood leukemia and causes abnormalities in cardiac and gastrointestinal formation. The average IQ of DS children is around 50. I would like to study why the gene triplication causes intellectual disability.
Mice are not humans, but they do have a mammalian genotype. The homologous region of human chromosome 21 in the mouse is mmu16. I am currently working with a mouse model that has the majority of mmu16 triplicated, Ts65Dn. This mouse model was developed in the early 90's. There are other models, including ones with less of mmu16 triplicated, and one that carries the actual human chromosome 21.
Studying this mouse model is not the same as studying humans with down syndrome, but it does give us a means to examine the development of the brain under similar conditions.
Mouse models of DS have revealed that less excitatory neurons develop in the forebrain of trisomic mammals, and that these neuron differentiate later in development. They also form less excitatory synapses and have more dendritic spine abnormalities. DS model mice also have more PARV and SOM positive cells from the Medial ganglion eminence. This basically indicates an overproduction of inhibitory neurons in the forebrain. One reason for the overproduction of inhibitory neurons might be that Olig1 and Olig 2 are not specifying MGE precursors into oligodendrocytes, thus leaving them to become inhibitory interneurons.
Myelination tends to occur later in the DS model mice, and the cerebellum of DS model mice is smaller with fewer purkinje neurons and only 2/3 of the normal number of granule cells.
One of the major challenges of studying the development of DS model mice is that triplication of various genes does not just affect the expression of those genes, but that it then affects the expression of euploid genes as well. Thus some phenotypes do not arise the same way in cultured cells.
More details to come on individual genes and transcription factors that may be relevant to the DS phenotype in the DS model mice.
