Molecular analysis of triosephosphate isomerase mutants with reduced enzyme activity in humans and mice
- Lawrence Livermore National Lab., CA (United States); and others
A series of variants, each characterized by the loss of function, have been identified at the triosephosphate isomerase (TPI) locus. Eight were identified in mouse germinal mutation experiments, while 12 were identified in screening a human newborns sample. Genomic PCR amplification products were sequenced to determine the molecular lesions. The ethylnitrosourea induced mouse mutants were found to be transversions. Tpi*M-1NEU, Tpi*M-2NEU and Tpi*M-4NEU were T:A and A:T substitutions. M-1NEU and M-2NEU were Leu to Gln substitutions at residue 192; M-4NEU was a Leu to Gln substitution at residue 162. The Tpi*M-3NEU allele was an A:T to C:G transversion changing the stop codon to Cys, resulting in the addition of 19 amino acids. Three different mutations have been identified in the eight human TPI-deficient probands characterized. A T:A to G:C transversion in the promoter region (TATA box) was identified. In 5 individuals a G:C to C:G transversion, substituting a Glu for a Gln at residue 104 was observed twice. Finally, a G:C to A:T transition at residue 160 led to a Val to Met substitution. These mutants provide insight into the mechanism of mutations and are models for structure-function studies of the interesting enzyme where most of the variants are null variants rather than electromorphs.
- OSTI ID:
- 135563
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1107
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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