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Sequence encoding the precursor protein signal sequence was replaced with a cassette containing beta-galactosidase and neomyicin resistance genes. Transcript was undetected by Northern blot analysis of intestinal and brain samples obtained from homozygous mutant mice. Similarly, radioimmunoassay of HPLC-fractioned brain extracts and immunohistochemical analysis of brain sections indicated an absence of normal protein. Expression of the beta-galactosidase gene was not detected by staining. (J:80590)