What is MLL mutation?
MLL rearrangements belong to type-II mutations [60] and lead to the impaired differentiation of hematopoietic cells. Type-I mutations mainly reflect molecular mutation hotspots in specific genes ( FLT3 , KIT , NRAS , KRAS , PTPN11 ), which are involved in the proliferation of hematopoietic cells [12].
What causes MLL?
(B) MLL fusion proteins are caused by chromosomal rearrangements leading to in-frame fusions between N-terminal MLL (to the BCR) and any of 80 different fusion partners. PHD domains, transactivation domains, and the SET domain are lost.
What does 11q23 mean?
11q23 translocations (t(11q23)) are recurring cytogenetic abnormalities in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia, involving the same gene, ALL1 (or MLL). Mixed lineage antigen expression has been reported in these leukemias, but its frequency and clinical significance are unknown.
What are the limitations of knockout mice?
While knockout mice technology represents a valuable research tool, some important limitations exist. About 15 percent of gene knockouts are developmentally lethal, which means that the genetically altered embryos cannot grow into adult mice.
Why are crossbreed mice not complete knockout?
Consequently, they are not complete knockout mice. It is necessary to crossbreed such mice to produce lines of mice in which both copies of the gene (one on each chromosome) are knocked out in all tissues. Researchers refer to such mice as homozygous knockouts.
How do you knockout mice?
To produce knockout mice, researchers use one of two methods to insert artificial DNA into the chromosomes contained in the nuclei of ES cells. Both methods are carried out in vitro, that is in cultured cells grown in laboratory conditions.
Why are ES cells used to make knockout mice?
ES cells are used because they are able to differentiate into nearly any type of adult cell, which means that if a gene is knocked out in an ES cell, the effects can be observed in any tissue in an adult mouse. In addition, ES cells grown in the lab can be used to make knockout mice as long as 10 years after they were harvested.