Generation of a panel of antibodies against proteins encoded on human chromosome 21

We attempted to generate human specific antibodies against proteins encoded by human chromosome 21. We selected proteins that are expressed in the adult brain of Tc1 mice and contain regions of moderate/low homology with the mouse ortholog. We produced antibodies to seven human chromosome 21 encoded proteins. Of these, we successfully generated three antibodies that preferentially recognise human compared with mouse SOD1 and RRP1 proteins on western blots. However, these antibodies did not specifically label cells which carry a freely segregating copy of Hsa21 in the brains of our Tc1 mouse model of DS.Although we have successfully isolated new antibodies to SOD1 and RRP1 for use on western blots, in our hands these antibodies have not been successfully used for immunohistochemistry studies. These antibodies are freely available to other researchers. Our data high-light the technical difficulty of producing species-specific antibodies for both western blotting and immunohistochemistry.Down syndrome (DS) is the most common genetic cause of intellectual disability and is also associated with a number of other medical problems including heart defects, early onset Alzheimer's disease and leukaemia [1]. DS is caused by trisomy of human chromosome 21 and is a complex genetic disorder in which the phenotype arises from abnormal dosage of otherwise normal genes.In order to investigate the relationship between phenotype and causative dosage sensitive genes in DS, we created the Tc1 mouse strain which carries a freely segregating copy of human chromosome 21 (Hsa21) in addition to a full complement of mouse chromosomes [2]. There are deletions in this Hsa21 [2] but at least 83% of the human genes are present in three copies (one human, two endogenous mouse homologs). Therefore, Tc1 mice are trisomic for the majority of genes on Hsa21 and several different investigations have shown they do indeed have phenotypes which are strikingly similar to those found in individuals with DS