ADD1, also known as adipocyte determination and differentiation-dependent factor 1, is a helix-loop-helix transcription factor. It is associated with adipocyte determination, differentiation, and fatty acid metabolism. ADD1/SREBP1c can activate the PGC1-alpha promoter in brown adipocytes, and ADD1 plays a role in insulin-induced gene expression linked to the MAP kinase pathway. It also activates PPARgamma through the production of endogenous ligand, thus being important in adipose differentiation and energy homeostasis [2,3,4,5,6].

Loss-of-function studies in Add1 knockout mice have shown that pathogenic ADD1 variants cause corpus callosum dysgenesis, ventriculomegaly, and/or intellectual disability in humans, indicating its crucial role in human neural development [1].

In conclusion, ADD1 is essential for adipocyte-related processes and neural development. The Add1 knockout mouse model has been instrumental in revealing its role in neural-related disease conditions, providing valuable insights into the mechanisms underlying these disorders.

References:

1. Qi, Cai, Feng, Irena, Costa, Ana Rita, Walsh, Christopher A, Zhang, Xiaochang. 2021. Variants in ADD1 cause intellectual disability, corpus callosum dysgenesis, and ventriculomegaly in humans. In Genetics in medicine : official journal of the American College of Medical Genetics, 24, 319-331. doi:10.1016/j.gim.2021.09.014. https://pubmed.ncbi.nlm.nih.gov/34906466/

2. Hao, Qin, Hansen, Jacob B, Petersen, Rasmus K, Madsen, Lise, Kristiansen, Karsten. 2009. ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes. In Biochimica et biophysica acta, 1801, 421-9. doi:10.1016/j.bbalip.2009.11.008. https://pubmed.ncbi.nlm.nih.gov/19962449/

3. Tontonoz, P, Kim, J B, Graves, R A, Spiegelman, B M. . ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. In Molecular and cellular biology, 13, 4753-9. doi:. https://pubmed.ncbi.nlm.nih.gov/8336713/

4. Kim, J B, Spiegelman, B M. . ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. In Genes & development, 10, 1096-107. doi:. https://pubmed.ncbi.nlm.nih.gov/8654925/

5. Kotzka, J, Müller-Wieland, D, Koponen, A, Knebel, B, Krone, W. . ADD1/SREBP-1c mediates insulin-induced gene expression linked to the MAP kinase pathway. In Biochemical and biophysical research communications, 249, 375-9. doi:. https://pubmed.ncbi.nlm.nih.gov/9712704/

6. Kim, J B, Wright, H M, Wright, M, Spiegelman, B M. . ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. In Proceedings of the National Academy of Sciences of the United States of America, 95, 4333-7. doi:. https://pubmed.ncbi.nlm.nih.gov/9539737/