Adnp2-KO Mouse

Adnp2, also known as KIAA0863 and ZNF508, is a member of the activity-dependent neuroprotective protein (ADNP) family. It contains a homeobox-profile and is evolutionarily conserved. Adnp2 is involved in multiple biological processes. It is expressed in oligodendrocytes and may impact myelin formation [2]. It also plays a role in the control of retrotransposons as part of the ChAHP2 complex, complementing the activity of the ChAHP complex which contains ADNP [3].

In genetic studies, adnp2 mutant zebrafish models generated using CRISPR/Cas9 technology exhibited developmental delays, brain deficits, and core behavioral features of neural developmental disorders (NDDs). RNA sequencing analysis of their larval brains revealed altered gene expression profiles affecting synaptic transmission, autophagy, apoptosis, microtubule dynamics, hormone signaling, and circadian rhythm regulation [1]. In mouse studies, silencing of Adnp2 in erythroleukemia cells inhibited erythroid maturation, similar to the effect of Adnp silencing, suggesting an ancestral role in erythropoiesis [4].

In conclusion, Adnp2 is important for neural development, myelin formation, and erythropoiesis, and its dysregulation may contribute to NDDs. The gene knockout models in zebrafish and mouse have been crucial in revealing these functions, providing insights into the underlying mechanisms of related diseases and potential therapeutic targets [1,2,3,4].

References:

1. Wang, Yongxin, Sun, Xiaoyun, Xiong, Bo, Duan, Ming, Sun, Yuhua. 2024. Genetic and Environmental Factors Co-Contributing to Behavioral Abnormalities in adnp/adnp2 Mutant Zebrafish. In International journal of molecular sciences, 25, . doi:10.3390/ijms25179469. https://pubmed.ncbi.nlm.nih.gov/39273418/

2. Malishkevich, Anna, Leyk, Janina, Goldbaum, Olaf, Richter-Landsberg, Christiane, Gozes, Illana. . ADNP/ADNP2 expression in oligodendrocytes: implication for myelin-related neurodevelopment. In Journal of molecular neuroscience : MN, 57, 304-13. doi:10.1007/s12031-015-0640-4. https://pubmed.ncbi.nlm.nih.gov/26315608/

3. Ahel, Josip, Pandey, Aparna, Schwaiger, Michaela, Hess, Daniel, Bühler, Marc. 2024. ChAHP2 and ChAHP control diverse retrotransposons by complementary activities. In Genes & development, 38, 554-568. doi:10.1101/gad.351769.124. https://pubmed.ncbi.nlm.nih.gov/38960717/

4. Dresner, Efrat, Malishkevich, Anna, Arviv, Carmit, Gothilf, Yoav, Gozes, Illana. 2012. Novel evolutionary-conserved role for the activity-dependent neuroprotective protein (ADNP) family that is important for erythropoiesis. In The Journal of biological chemistry, 287, 40173-85. doi:10.1074/jbc.M112.387027. https://pubmed.ncbi.nlm.nih.gov/23071114/