of protein known as inclusion bodies. While the cDNA may properly code for a translatable mRNA, the protein that results will emerge in a foreign microenvironment. This often has fatal effects, especially if the intent of cloning is to produce a biologically active protein. For example, eukaryotic systems for carbohydrate modification and membrane transport are not found in prokaryotes. The internal microenvironment of a prokaryotic cell (pH, osmolarity) may differ from that of the original source of the gene. Mechanisms for folding a protein may also be absent, and hydrophobic residues that normally would remain buried may be exposed and available for interaction with similar exposed sites on other ectopic proteins. Processing systems for the cleavage and removal of internal peptides would also be absent in bacteria. The initial attempts to clone insulin in a bacterium suffered all of these deficits. In addition, the fine controls that may keep the concentration of a protein low will also be missing in a prokaryotic cell, and overexpression can result in filling a cell with ectopic protein that, even if it were properly folded, would precipitate by saturating its environment. In neurons Inclusion bodies are aggregates of protein associated with many neurodegenerative diseases, accumulated in the cytoplasm or nucleus of neurons. Inclusion bodies of aggregations of multiple proteins are also found in muscle cells affected by inclusion body myositis and hereditary inclusion body myopathy. Inclusion bodies in neurodegenerative diseases are aggregates of misfolded proteins (aggresomes) and are hallmarks of many of these diseases, including Lewy bodies in Lewy body dementias, and Parkinson's disease, neuroserpin inclusion bodies called Collins bodies in familial encephalopathy with neuroserpin inclusion bodies, inclusion bodies in Huntington's disease, Papp-Lantos inclusions in multiple system atrophy, and various inclusion bodies in frontotemporal dementia including Pick bodies. Bunina bodies in motor neurons are a core feature of amyotrophic lateral sclerosis. In red blood cells Normally a red blood cell does not contain inclusions in the cytoplasm. However, it may be seen because of certain hematologic disorders. There are three kinds of red blood cell inclusions: Developmental organelles Howell-Jolly bodies: small, round fragments of the nucleus resulting from karyorrhexis or nuclear disintegration of the late reticulocyte and stain reddish-blue with Wright's stain. Basophilic stipplings - these stipplings are either fine or coarse, deep blue to purple staining inclusion that appears in erythrocytes on a dried Wright's stain. Pappenheimer bodies - are siderotic granules which