DATA RELEASE – MAY 2016


New DMDD data is now available on our website. This week we’ve added HREM embryo image stacks for 12 new lines, embryo phenotype data for 12 lines and placental phenotype data for a further 10 lines.

For full details on what we’ve released see the bottom of this post, or look at our updates page.  But here are a few highlights we found while reviewing the data.

 

EMBRYO PHENOTYPES

Our embryo phenotyping team were particularly interested in the lines Smg9 and Col4a3bp.

Smg9 showed malformations affecting several organ systems. The most prominent were malformations in the nervous system (including exencephaly) and in the cardiovacular system. This data release includes phenotype annotations for 6 embryos in the Smg9 line, meaning that penetrance data can be explored for the related phenotypes.

An embryo with a mutation of the gene Smg9 displays exencephaly.

An embryo with a mutation of the gene Smg9 displays exencephaly.

Line Col4a3bp showed malformations of the cardiovascular system and the axial skeleton.

 

PLACENTAL DATA

Our placenta team highlighted Brd2, a transcriptional regulator belonging to the therapeutically important BET (bromodomains and extra terminal domain) family of proteins with epigenetic functions.

As well as exhibiting severe growth retardation, placentas from this line showed a massively reduced vascular density that will result in insufficient nutrient supply to the embryo.

Brd2 placentas display reduced vascular density.

A comparison of wild-type and mutant placentas for the line Brd2 shows reduced vascular density in the mutant placentas.

 

The Brd2 line is also interesting from the point of view of mouse production. When the DMDD programme began back in 2013, all our knockout mouse lines were made using embryonic stem cells. Our partners at the Wellcome Trust Sanger Institute have recently begun using the CRISPR-Cas9 technique for creating knockout mice, and Brd2 is the first of these lines to make its way to the DMDD analysis pipeline.

 

CLINICAL INTEREST

Many of the genes studied by DMDD have human orthologues, mutations in which are related to known conditions. DMDD data is a way to examine, in great detail, the resulting phenotypes when these genes are knocked out in a mouse model.

New lines that may be relevant to clinicians (although not an exhaustive list) are:

Col4a3bp: in humans, diseases associated with COL4A3BP include mental retardation, autosomal dominant 34 and goodpasture syndrome.

Ssr2: the human ortholog of this gene is associated with calcaneonavicular coalition.

Trappc9: in humans, diseases associated with TRAPPC9 include intellectual disability, obesity, brain malformations, facial dysmorphism and Birk-Barel mental retardation dysmorphism syndrome.

 

A FULL LIST OF NEW DATA

HREM image data: Brd2, Camsap3, Col4a3bp, Cpt2, Eif3h, H13, Mir96, Npat, Nsun2, Pdzk1, Smg9, Trim45.

Embryo phenotype data: Adamts3, Camsap3, Col4a3bp, Dbn1, Duoxa2, Exoc3l2, Ogdh, Slc5a7, Smg9, Ssr2, Traf2, Trappc9.

Placental phenotype data: Brd2, Cnot4, Cog6, Col4a3bp, Cpt2, Cyp11a1, Pdzk1, Pgap2, Smg9, Wrap53.

Data is searchable by both gene and phenotype, and all image data can be viewed online at full resolution. To request the data offline, or for any enquiries please get in touch: contact@dmdd.org.uk.


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