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| Nomenclature |
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Symbol:
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hph1
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Name:
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hyperphenylalaninemia 1
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MGI ID: |
MGI:1856903 |
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Synonyms: |
hph-1 |
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Gene:
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hph1
Location:
unknown
Genetic Position: Chr14,
Syntenic
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Mutation
origin |
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Strain of Origin:
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(C57BL/6 x CBA/Ca)F1
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Mutation
description |
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Allele
Type: | |
Chemically induced (ENU) |
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Mutation: | |
Undefined |
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Mutation details: It appears that hph1 may be a mutation in the mouse GTP cyclohydrolase gene, Gch1, although there are no coding sequence changes in the Gch1 open reading frame in hph1 mutants (J:20569). Homozygous mice carrying this mutation express significanly lower levels of GTP cyclohydrolase. (J:20569)
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Inheritance: | |
Recessive |
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Phenotypes
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View phenotypes for all genotypes (concatenated display).
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Disease models
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| Find Mice (IMSR) |
Mouse strains and cell lines available from the
International Mouse Strain Resource
(IMSR)
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Carrying this Mutation: |
Mouse Strains: 0 strains available
Cell Lines: 0 lines available |
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Carrying any hph1 Mutation:
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0 strains or lines available |
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Notes |
This mouse mutation, which causes hyperphenylalaninemia, does not affect the gene encoding PAH. PAH activity is only a slightly reduced, not sufficiently to cause a PKU phenotype (J:9146). Mutant animals respond to the administration of BH4, and their livers are deficient in this coenzyme. DHPR is present in normal quantities in these animals, but GCH activity is practically absent in young hph1/hph1 homozygotes, and greatly reduced in older animals. Heterozygotes are intermediate in activity between homozygous normal and hph1 homozygotes. Thus, GCH deficiency seems to be the underlying cause of HPH in hph1 mutant mice (J:8982).
BH4 is also a cofactor for tryptophane hydroxylase and tyrosine hydroxylase, which are rate limiting enzymes in the synthesis of serotonin and dopamine. The hph1 mutation has been associated with reduced levels of these substances and their metabolites in liver and brain. It has been suggested that neuropathological mechanisms in dopa-responsive dystonia are related to BH4 activity, and are amenable to study in hph1 mice (J:34167). The nitric oxide synthase activity of hph1 mice is impaired, suggesting that BH4 is a cofactor for this enzyme as well (J:35898).
It appears that hph1 may be a mutation in the mouse GTP cyclohydrolase gene, Gch1, although there are no coding sequence changes in the Gch1 open reading frame in hph1 mutants (J:20569).
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| References |
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Original: |
J:9146
Bode VC et al.,
"hph-1: a mouse mutant with hereditary hyperphenylalaninemia induced by ethylnitrosourea mutagenesis."
Genetics 1988 Feb;118(2):299-305
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All: |
22 reference(s)
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Analysis Tools
