Investigation Of Dip2a And Dip2b Gene Functions

Disco-Interacting Protein 2 Homolog A?DIP2A?is a member of DIP2 protein family,encoded by the Dip2a gene.Our laboratory has generated Dip2a-LacZ report gene transgenic mice model which reveals the endogenous Dip2a gene expression pattern.The specific biological function of Dip2a gene is still not clear now and we also using CRISPR/Cas9technology generated a Dip2a?65kb knockout mice model.The above two knockout mice models were used to study the histological differences of tissues and organs,which may tell us the Dip2a gene specific physiological functions.By comparing the H&E results of different organs we found that after Dip2a knockout,part of mouse cerebellar Purkinje cells arranged irregular,the cell body direction is inconsistent,shorter dendrites and fewer branches.We also found increasing in the number of megakaryocyte number in spleen.At the same time the appearance of red pulp and white pulp is not obvious.These differences suggest that Dip2a gene may be involved in the synapses formation,axon guidance,immune process and so on.DIP2B,also a DIP2 protein family member,has been showed to be associated with a human mental disease,and its endogenous physiological function is still not clear.We have been using our Dip2b-LacZ gene reporter mice model to study Dip2b endogenous expression patterns and its specific physiological functions.LacZ staining showed that Dip2b gene in the mouse embryo is widely expressed in all organs,suggesting that Dip2b gene may play an important role for mouse embryonic organ development.H&E staining showed that the Dip2b knockout mice lung was immature.The lung epithelial cells were hyperplasia,and thickening of alveolar between the diaphragm and alveolar space was observed.Dip2b knockout will result in fetus intrauterine growth retardation,and pups will die around 4hours after birth due to pulmonary or cardiovascular defects.The similar defects of Dip2b^-/-and Fstl1^-/-lungs suggests that DIP2B but not DIP2A might be the biological receptor of FSTL1in mice.DIP2A and DIP2B have very high similarity in amino acid sequences and protein structures which indicating that they may have a similar physiological functions,and may have a compensatory role for each other.We therefor generated Dip2a^?65kb/?65kb;Dip2b^LacZ/WTacZ/WT mouse model which could be used to analyze the phenotype of adult mouse nervous system,or use to obtain Dip2a^?65kb/?65kb;Dip2b^LacZ/LacZ embryos for phenotyping.The double knockout mice models will be useful for us to elucidate the physiological function of DIP2 proteins.