Biomedical subjects
Publications and source records attributed to M Budarf.
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The initial steps in the processing of the common precursor to adrenocorticotropin (ACTH) and beta-lipotropin (beta-LPH) in mouse pituitary cells (AtT-20) have been investigated. Three forms of the precursor have been resolved by sodium dodecyl sulfate (NaDodSO4) polyacrylamide gel electrophoresis with apparent molecular weights of 29,000, 32,000 and 34,000 (29K, 32K, and 34K ACTH-endorphin). The three precursor forms have a very similar peptide backbone, but their carbohydrate content differs. In particular, a tryptic glycopeptide has been observed in 32K ACTH-endorphin which is not present in 29K ACTH-endorphin and has been identified as a tryptic peptide containing the alpha(22--39) sequence of ACTH. Pulse chase and continuous-labeling studies with radioactive amino acids and sugars suggest that the 29K form is converted to the 32K and 34K forms of the precursor by the addition of carbohydrate. The glycopeptide and pulse chase studies suggest that 29K ACTH-endorphin can either be converted to 4.5K ACTH by proteolytic processing or to 32K ACTH-endorphin by the further addition of carbohydrate.
Conotruncal defects (CTDs) of the heart are a frequent component of DiGeorge, velocardiofacial, or other syndromes caused by deletions of the human chromosome 22q11 region (HSA22q11). In addition, some human patients with isolated nonsyndromic CTDs have been reported to have deletions of this region. Taken together, these findings lead to the conclusion that deletions of an HSA22q11 locus or loci produce abnormalities in cardiac development leading to CTDs. A spontaneous model of isolated inherited conotruncal malformations occurs in the keeshond dog. We have previously shown in experimental matings that nonsyndromic CTDs in the keeshond are inherited in a manner consistent with a major underlying locus. In the studies described in this article we tested two hypotheses: (1) the region of HSA22q11 commonly deleted in DiGeorge and related syndromes is evolutionarily conserved in the dog, and (2) a locus in this region is linked to hereditary CTD in the keeshond. Two loci within the minimal DiGeorge critical region (MDGCR) and two loci that lie telomeric to the MDGCR, one of which is commonly deleted in DiGeorge patients, were mapped in the dog using a combination of linkage analysis and fluorescence in situ hybridization (FISH). The results confirm conserved synteny of the loci DGS-I, CTP, D22S788 (N41), and IGLC on the telomeric end of canine chromosome 26 (CFA26). The group of four syntenic gene loci, which spans a genetic distance of 2.5 cM is the first to be mapped to this small acrocentric canine chromosome and adds gene-associated polymorphic markers to the developing dog linkage map. Linkage of loci in this region to hereditary CTD in the keeshond was excluded.