Researchers find new genetic information behind urogenital track anomalies

Researchers at the University of Helsinki have developed a new mouse model of congenital anomalies of kidney and urinary tract and disease progression.

About one in every 100 babies is born with some kind of developmental anomaly in the urogenital tract. In most cases abnormalities are mild, but sometimes life-long and even life-threatening disease develops.

Infertility is another important aspect that associates with urogenital anomalies. Therefore understanding how those features occur is instrumental in developing future treatments.

To date, diseases which scientist understand the best are those caused by mutations in the proteins involved. However, in many diseases such mutations are not found, and the disease is “idiopathic” or referred as without a known cause, and maybe triggered by e.g. environmental factors.

Classically scientists have studied such cases by injecting many copies of the gene of interest into fertilized egg of an experimental animal. However, the major problem with this technique is that scientist have almost no control over where in the genome the gene lands, and what cell types start to produce the encoded protein.

By employing an unconventional genome engineering trick that increased glial cell line-derived neurotrophic factor (GDNF) production 3-6 times, scientists revealed that ureter, which allows urine produced by kidneys to enter bladder, length is regulated by GDNF levels, and that tubes connecting testicles to reproductive organs are misplaced when there is too much GDNF, resulting in infertility in males.

GDNF is a secreted protein which signals growth and survival for many types of cells. In females, too much GDNF resulted in imperforated vagina or lack of vaginal opening, resulting in infertility.

The researchers were able to trace some of those defects back to altered stem cell behaviour in the developing urogenital block and identified some signalling pathways involved. Collectively these findings provide new information on altered stem cell behaviour in the developing kidney.

University of Helsinki

https://tinyurl.com/y6oag6xr