`University of Pittsburgh researchers have developed a genetically modified mouse line carrying 46 genes coding for primate specific micro-RNAs (miRNAs), referred to as the chromosome 19 microRNA cluster (C19MC) due to being located on chromosome 19.q13 in humans. The expression of C19MC in mice could enable scientists to gain a deeper understanding of a variety of medical conditions including pediatric brain tumors.
Description
C19MCs are normally only expressed in the placenta during pregnancy, but abnormal expression has been associated with rare forms of cancers, particularly pediatric brain tumors. This mouse model, the first non-primate model ever developed expressing C19MC could allow for researchers to better study the role of these genes in various conditions.
Applications
• Pediatric health
• Fetal development
• Maternal/fetal communication
Advantages
While the expression pattern of C19MC is almost exclusively in the placenta accounting for nearly 40% of miRNAs present in trophoblasts, it is of note that abnormal expression is associated with some uncommon cancers. The function of these miRNAs and their role in cancer development remains poorly understood. Better models are needed to truly understand any role of these miRNAs in fetal development and maternal health.
These mice, the first non-primate model of this type, are designed to produce human C19MC miRNAs recapitulating their characteristic placental expression allowing for better study of the miRNA role in fetal development, maternal health, and some tumors.
Invention Readiness
Transgenic mice were generated following pronuclear microinjection of supercoiled Bacterial Artificial Chromosome (BAC) DNA containing the entire human C19MC locus including an upstream regulatory sequence into mice embryos. Compared with wild type (WT) mice, there was no significant difference in anatomy, or placental messenger RNA expression.
Studies using these transgenic mice have demonstrated increased expression of C19MC (>40-fold) in the placenta of pregnant mice, resembling expression patterns in humans. Experiments using homozygous transgenic mice (dTG) identified several genes that were differentially expressed compared to WT mice, which could impact on the specification and development of placental cell layers. Additionally, these mouse models found miRNA could traffic between the placenta, fetal compartment, and maternal circulation suggesting an extraordinary means of nonhormonal, miRNA-based communication between the placenta and feto-maternal compartments. Further research could build on this discovery to develop blood-based diagnostics of pregnancy complication related to placental dysfunction.
IP Status
Research Tool
