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Rewriting Life

Mimicking Autism

Mice lacking a specific piece of DNA show symptoms like those in humans

Source: “Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism”
Alea A. Mills, Michael Wigler, et al.
Proceedings of the National Academy of Sciences
108: 17076–17081

Results: Scientists engineered mice whose DNA had deletions or duplications at a specific site that has previously been linked to autism and schizophrenia. Animals in which this chromosome section was missing showed behaviors associated with autism, such as repetitive movements and sleep problems. In contrast, mice with an extra copy of this region slept more. Those with the deletion also had a larger hypothalamus, the part of the brain that controls eating and sleep.

Why it matters: The animals with the deletion will help scientists study the effects of this abnormality on all stages of brain development, which could in turn shed light on neurological deficits underlying autism. Researchers also hope to find early biomarkers of autism that could be used to help diagnose the disorder.

This story is part of our January/February 2012 Issue
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Methods: The researchers used chromosome engineering to create mice with the deletion or duplication on chromosome 16. To precisely track the animals’ movement, they used an infrared camera system. MRI scans were used to determine the volume of different parts of the brain.

Next steps: The section of chromosome 16 under study includes 27 genes. In order to identify the genes responsible for the autism-like features, the researchers plan to ­create mice with missing or extra copies of different subsections of this chromosome segment.

Predicting Response to Cancer Treatment

A new test could make chemotherapy more effective

Source: “Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy”
Anthony Letai et al.
, published online October 27, 2011

Results: Researchers at the Dana-Farber Cancer Institute found that tumor cells were more likely to respond to chemotherapy if they were on the verge of apoptosis, which is one of the ways that cells die. In addition, they found that an experimental drug under development by Abbott Labs, which drives cells toward apoptosis, makes cells more sensitive to three different chemotherapy drugs.

Why it matters: The findings show that some tumors are closer to apoptosis than others. This information could help doctors identify those patients most likely to respond to chemotherapy, which can have toxic side effects. It could also help scientists develop drugs that make chemotherapy more effective by pushing cancer cells toward apoptosis, a natural part of the cell life cycle that is known to go awry in cancer.

Methods: ­Researchers collected live cancer cells from patients with multiple myeloma, acute myelogenous leukemia, and ovarian cancer. They then exposed the cells to protein fragments that promote apoptosis. In the cells that were already close to death, these fragments damaged the mitochondria. The researchers correlated the degree of damage with the patients’ response to chemotherapy.

Next steps: Anthony Letai, the researcher who led the study, has cofounded a startup called Eutropics Pharmaceuticals, which has licensed the technology and is planning clinical trials in cancer patients.

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