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Gene Responsible For Mammary Gland Function, When Mutated Results in Leukemias

s a group of specific genes that cooperate to perform a particular function. The group of genes activated by SRF depends on which member of the MKL1 family binds to the SRF protein.

This MKL1-linked SRF pathway is one of two such cellular signaling cascades of biochemical reactions that enable SRF to activate specific genes, according to Morris. The other pathway uses a group of three proteins collectively called TCF. These proteins help SRF bind to SRE DNA sequences and activate the expression of other genes. 'The MKL1 protein is normally active relatively widely throughout the body,' Morris said. 'So we were surprised that the loss of the MKL1 gene had such a limited effect.

This probably reflects the fact that the other two protein members of the MKL1 family also can trigger the SRF pathway, as can TCF.' To study the role of MKL1, the team produced genetically modified mouse embryos that lacked the MKL1 gene (MKL1 -/- mice) and observed what happened in the mice when the gene was absent. The investigators reported that about 40 percent of mouse embryos that lacked MKL1 did not survive to birth, although the mice that did survive appeared normal.

However, the female mice that survived and grew to adulthood were not able to successfully nurse their offspring because they lacked MKL1 and were not able to expel milk from their mammary glands. 'The absence of the MKL1 gene impairs normal development and function of mammary gland muscle genes that depend on SRF,' Morris said. 'These muscles are the ones that contract and cause milk ejection in response to nursing.’ The St. Jude team further demonstrated the normal role of MKL1 by using ‘gene chips' to analyze mammary tissues in MKL1 -/- mice.

The researchers found that there was a significant reduction in activity of a group of genes linked to the development and differentiation (specialization of cells) of the myoepithelial muscle cells in the mammary gland. These muscles, whic
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