Project description:Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) (OMIM 618278) is a rare infantile-onset disease caused by variants in NHL repeat containing 2 (NHLRC2) gene. NHLRC2 is essential for mouse gastrulation (Hiltunen et al., 2022). Here, RNA sequencing was performed on four wild type (WT), four homozygous C57BL/6NCrl-Nhlrc2em1Rthl (FINCA disease causing variant) (Hiltunen et al., 2020), and four homozygous C57BL/6NCrl-Nhlrc2tm1a(KOMP)Wtsi (Nhlrc2 knock out) mouse embryonic stem cell lines each established from individual mouse embryos by the 2i method (Nichols et al., 2009). FINCA variant mESCs express the full length endogenous Nhlrc2 mRNA modified to containing a c.442G > T variant leading to p.Asp148Tyr as well as a silent c.408C>A for genotyping purposes (Hiltunen et al., 2020). In the Nhlrc2 KO mESCs the transcription is halted by a trapping cassette between exons 4 and 5 (Hiltunen et al., 2022; Skarnes et al., 2011). References Hiltunen, A. E., Kangas, S. M., Ohlmeier, S., Pietilä, I., Hiltunen, J., Tanila, H., McKerlie, C., Govindan, S., Tuominen, H., Kaarteenaho, R., Hallman, M., Uusimaa, J., & Hinttala, R. (2020). Variant in NHLRC2 leads to increased hnRNP C2 in developing neurons and the hippocampus of a mouse model of FINCA disease. Molecular Medicine, 26(1), 123. https://doi.org/10.1186/s10020-020-00245-4 Hiltunen, A. E., Vuolteenaho, R., Ronkainen, V. P., Miinalainen, I., Uusimaa, J., Lehtonen, S., & Hinttala, R. (2022). Nhlrc2 is crucial during mouse gastrulation. Genesis, 60(3), e23470. https://doi.org/10.1002/dvg.23470 Nichols, J., Silva, J., Roode, M., & Smith, A. (2009). Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo. Development (Cambridge), 136(19), 3215–3222. https://pubmed.ncbi.nlm.nih.gov/19710168/ Skarnes, W. C., Rosen, B., West, A. P., Koutsourakis, M., Bushell, W., Iyer, V., Mujica, A. O., Thomas, M., Harrow, J., Cox, T., Jackson, D., Severin, J., Biggs, P., Fu, J., Nefedov, M., de Jong, P. J., Stewart, A. F., & Bradley, A. (2011). A conditional knockout resource for the genome-wide study of mouse gene function. Nature, 474(7351), 337–342. https://doi.org/10.1038/nature10163
2025-05-22 | E-MTAB-14174 | biostudies-arrayexpress
Lihini Aluwihare 
