JOURNAL ARTICLE

A GRM7 mutation associated with developmental delay reduces mGlu7 expression and produces neurological phenotypes

Nicole M Fisher, Aqeela AlHashim, Aditi B Buch, Hana Badivuku, Manar M Samman, Kelly M Weiss, Gabriela I Cestero, Mark D Does, Jerri M Rook, Craig W Lindsley, P Jeffrey Conn, Rocco G Gogliotti, Colleen M Niswender
JCI Insight 2021 January 21
33476302
The metabotropic glutamate receptor 7 (mGlu7) is a G protein-coupled receptor that has been recently linked to neurodevelopmental disorders. This association is supported by the identification of GRM7 variants in patients with autism spectrum disorder, attention deficit hyperactivity disorder, and severe developmental delay. One GRM7 mutation previously reported in two patients results in a single amino acid change, I154T, within the mGlu7 ligand-binding domain. Here, we report two new patients with this mutation who present with severe developmental delay and epilepsy. Functional studies of the mGlu7-I154T mutant reveal that this substitution results in significant loss of mGlu7 protein expression in HEK293A cells and in mice. We show that this occurs post-transcriptionally at the level of protein expression and trafficking. Similar to mGlu7 global knockout mice, mGlu7-I154T animals exhibit reduced motor coordination, deficits in contextual fear learning, and seizures. This provides the first functional evidence that a disease-associated mutation affecting the mGlu7 receptor is sufficient to cause neurological dysfunction in mice and further validates GRM7 as a disease-causing gene in the human population.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
33476302
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"