PMID- 10441733 OWN - NLM STAT- MEDLINE DCOM- 19990923 LR - 20220223 IS - 0938-8990 (Print) IS - 0938-8990 (Linking) VI - 10 IP - 9 DP - 1999 Sep TI - Genomic organization and expression analysis of mouse kynurenine aminotransferase II, a possible factor in the pathophysiology of Huntington's disease. PG - 845-52 AB - Decreased levels of the endogenous neuroprotectant kynurenic acid (KYNA) have been observed in the brain of Huntington's Disease (HD) patients and may be related to neuronal loss in this disorder. This reduction may be caused by a dysfunction of kynurenine aminotransferase II (KAT II), the major enzyme responsible for the synthesis of KYNA in the brain. Towards understanding the role of KAT II in HD, we isolated and characterized the cDNA sequence and determined the genomic organization of mouse KAT II (mKat-2). The full length mKat-2 cDNA is 1812 bp, encoding 425 amino acids, and shares 89.9% amino acid similarity with the rat Kat-2 sequence. The gene for mKat-2 is composed of 13 exons divided by 12 intronic sequences. Northern blot analysis demonstrated that mKat-2 mRNA is mainly expressed in kidney and liver. RT-PCR showed mKat-2 expression in the brain starting from at least d11 of embryonic development. An alternative isoform mKat-2beta, derived from the usage of novel exons, shows a different expression pattern from mKat-2. Western blot analysis of various mouse tissues shows a 40-kDa protein in brain, heart, kidney, and liver. In the kidney and liver an additional 45-kDa isoform was detected. Use of the BSS chromosomal mapping panel from The Jackson Laboratory indicates that the mKat-2 gene co-segregates with polymorphic markers D8Mit129 and D8Mit128 on mouse Chr 8. Knowledge of the genomic organization, the isoform tissue-specific expression patterns, the chromosomal localization of mKat-2, and the reagents generated here, will provide the tools for further studies and allow generation and characterization of mice that are nullizygous for mKat-2. FAU - Yu, P AU - Yu P AD - Genetics and Molecular Biology Branch, National Human Genome Research Institute, Building 49, Room 3A26, 49 Convent Drive MSC 4442, National Institutes of Health, Bethesda, Maryland 20892-4442, USA. FAU - Mosbrook, D M AU - Mosbrook DM FAU - Tagle, D A AU - Tagle DA LA - eng SI - GENBANK/AF072376 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mamm Genome JT - Mammalian genome : official journal of the International Mammalian Genome Society JID - 9100916 RN - 0 (DNA Primers) RN - 0 (DNA, Complementary) RN - 0 (Isoenzymes) RN - 0 (RNA, Messenger) RN - EC 2.6.1.- (Transaminases) RN - EC 2.6.1.64 (glutamine - phenylpyruvate transaminase) RN - EC 2.6.1.7 (kynurenine-oxoglutarate transaminase) RN - EC 4.- (Lyases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Brain/enzymology MH - Chromosome Mapping MH - DNA Primers/genetics MH - DNA, Complementary/genetics/isolation & purification MH - Exons MH - Gene Expression MH - Genome MH - Humans MH - Huntington Disease/*enzymology/*genetics MH - Introns MH - Isoenzymes/*genetics MH - Kidney/enzymology MH - Liver/enzymology MH - *Lyases MH - Mice MH - Molecular Sequence Data MH - Promoter Regions, Genetic MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Sequence Homology, Amino Acid MH - Tissue Distribution MH - Transaminases/*genetics EDAT- 1999/08/12 00:00 MHDA- 1999/08/12 00:01 CRDT- 1999/08/12 00:00 PHST- 1999/08/12 00:00 [pubmed] PHST- 1999/08/12 00:01 [medline] PHST- 1999/08/12 00:00 [entrez] AID - MG99-653 [pii] AID - 10.1007/s003359901102 [doi] PST - ppublish SO - Mamm Genome. 1999 Sep;10(9):845-52. doi: 10.1007/s003359901102.