Trappc6a-KO Mouse

Trappc6a, a subunit of the transport protein particle (TRAPP) I and II complexes, is crucial for vesicle trafficking, which is essential for various cellular functions including protein sorting and secretion [2]. The TRAPP complexes are involved in ER-to-Golgi and intra-Golgi vesicle trafficking in yeast, and in mammals, they participate in additional post-Golgi transport events [2].

In a consanguineous family of Saudi origin, a homozygous mutation in Trappc6a was identified in patients with a neurodevelopmental syndrome involving intellectual disability, speech delay, facial dysmorphism, and polydactyly [1]. In the mhyp mouse model, a defect in Trappc6a led to mosaic hypopigmentation due to diminished gene expression, implicating Trappc6a in vesicle trafficking during melanosome biogenesis [2]. In a humanized yeast model, Trappc6a was found to successfully replace its yeast counterpart, and this system can be used to study Trappc6a variants when human cells are unavailable [3]. In patients with TRAPPC6B-related neurodevelopmental disorders, the levels of TRAPPC6A were elevated, suggesting a potential compensatory mechanism or functional interplay within the TRAPP complex [4].

In conclusion, Trappc6a is essential for vesicle trafficking, which impacts processes like melanosome biogenesis and is associated with neurodevelopmental syndromes. Mouse and yeast models have been valuable in uncovering Trappc6a's role in these biological processes and disease conditions, highlighting its significance in understanding normal development and related disorders.

References:

1. Mohamoud, Hussein Sheikh, Ahmed, Saleem, Jelani, Musharraf, Goodbourn, Steve, Nasir, Jamal. 2018. A missense mutation in TRAPPC6A leads to build-up of the protein, in patients with a neurodevelopmental syndrome and dysmorphic features. In Scientific reports, 8, 2053. doi:10.1038/s41598-018-20658-w. https://pubmed.ncbi.nlm.nih.gov/29391579/

2. Gwynn, Babette, Smith, Richard S, Rowe, Lucy B, Taylor, Benjamin A, Peters, Luanne L. 2006. A mouse TRAPP-related protein is involved in pigmentation. In Genomics, 88, 196-203. doi:. https://pubmed.ncbi.nlm.nih.gov/16697553/

3. Zykaj, Erta, Abboud, Chelsea, Asadi, Paria, Pérez-Jurado, Luis Alberto, Sacher, Michael. 2024. A Humanized Yeast Model for Studying TRAPP Complex Mutations; Proof-of-Concept Using Variants from an Individual with a TRAPPC1-Associated Neurodevelopmental Syndrome. In Cells, 13, . doi:10.3390/cells13171457. https://pubmed.ncbi.nlm.nih.gov/39273027/

4. Almousa, Hashem, Lewis, Sara A, Bakhtiari, Somayeh, Sacher, Michael, Kruer, Michael C. . TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions. In Brain : a journal of neurology, 147, 311-324. doi:10.1093/brain/awad301. https://pubmed.ncbi.nlm.nih.gov/37713627/