Researchers have created a mouse model of the heart defects that
occur in Down syndrome, by making a mouse with an extra copy of
many of the genes that correspond to the human genes on chromosome
21.
Down syndrome is the most common genetic cause of both
intellectual disability and heart defects in humans, and is
triggered by an extra copy of chromosome 21.
The work was led by Prof Victor Tybulewicz of the Francis Crick
Institute and Imperial College London and Prof Elizabeth Fisher of
University College London. Prof Tybulewicz explained: "The genetic
change in Down Syndrome results in a complex condition that is
characterised by learning difficulties, congenital heart defects,
increased rates of leukaemia and early onset Alzheimer's disease,
among others."
"Each of these different symptoms is caused by the extra
chromosome, and presumably by an extra copy of one or more of the
230 or so genes on the chromosome. However it is not known which
genes on chromosome 21 cause which defects."
The mouse model has allowed the team to visualise the detail of
how the defects occur during embryonic development.
The scientists made a series of mouse strains, each with extra
copies of different sets of mouse genes corresponding to the human
genes on human chromosome 21. This enabled them to narrow down the
genes that cause heart defects to 39 of the 230 genes on the
chromosome. It also allowed them to show that at least two
different genes contribute to the heart defects.
Dr Tybulewicz said: "This work is a major scientific advance. It
provides important insights into the genetic basis of Down
syndrome, and our panel of seven genetically engineered mouse
strains will help others to identify genes that cause other Down
syndrome symptoms.
The paper, Genetic dissection of Down
syndrome-associated congenital heart defects using a new mouse
mapping panel, is published in eLife.