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PETBioNewsNewsCleft lip genetically repaired in mice

BioNews

Cleft lip genetically repaired in mice

Published 17 January 2013 posted in News and appears in BioNews 636

Author

Rosemary Paxman

Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the output from a DNA sequencing machine.
CC BY 4.0
Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the sequencing output from an automated DNA sequencing machine.

Scientists have genetically repaired cleft lip and palate in mouse embryos in a breakthrough that could pave the way for new treatments of the common birth defects in humans...

Scientists have genetically repaired cleft lip and palate in mouse embryos in a breakthrough that could pave the way for new treatments of the common birth defects in humans.

The team, from Weill Cornell Medical College, identified mutations in the Pbx family of genes that resulted in complete cleft lip, with or without cleft palate.

These genes produce proteins which have previously been identified as playing a part in skeletal and organ development, but study author Dr Licia Selleri says that their role in face shape is a 'new and surprising finding'.

They found Pbx genes regulate a signalling pathway that includes a number of proteins known to be involved in cleft lip formation. By restoring the activity of one gene, known as Wnt, which plays a prominent role in embryo development, the researchers were able to repair cleft lips in mouse embryos.

'To my knowledge, this is the first time that anyone has corrected this defect in embryos, and we really show here that Wnt is a critical factor', explains Dr. Selleri. 'This is a very provocative result because it opens a completely new avenue of strategies for tissue repair'.

This development could help to prevent such defects or be used as a non-surgical treatment after birth.

With almost one in every 700 newborns having cleft lip or cleft palate, they are among the most common birth defects worldwide. Current treatment requires multiple surgeries, speech therapy and dental work.

Presently, there are very few pre-clinical methods which permit researchers to study the molecular causes of such defects. The lack of animal models that accurately reflect the contribution of multiple genes to these congenital deformities in humans poses further difficulties.

Following these promising results, the use of such techniques in humans is under investigation. Dr Selleri intends to examine the addition of Wnt molecules to Pbx-mutated mouse embryos within an environment mimicking the uterus, to see whether this is enough to prevent or correct the defects.

Dr Selleri says: 'Compared with genetic manipulations, this approach of delivering Wnt signals directly to the uterus would be more realistic for implementation in humans'.

The research is published in Developmental Cell.

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CC0 1.0
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