Disease relevance of Hsdr1

• We conclude that the neonatal lethal and liver dysfunction phenotype of the alf/hsdr-1 deletion is entirely attributable to loss of Fah [1].

High impact information on Hsdr1

• This phenotype is thought to result from the loss of a positive transacting factor, denoted alf, in deletion homozygotes [2].
• Surprisingly, a subset of these alf-responsive genes is negatively controlled by the tissue-specific extinguisher locus Tse-1 [2].
• On the basis of this phenotype, it was proposed that these deletions remove a regulatory locus, alf or hsdr-1 [3].
• Mice homozygous for albino deletions encompassing the locus alf/hsdr-1 die shortly after birth [4].
• Mechanisms by which this metabolic defect might bring about alterations in gene expression characteristic of the alf/hsdr-1 deletion phenotype are discussed [4].

Biological context of Hsdr1

• Here, we describe a detailed analysis of the region containing alf/hsdr-1 by means of chromosome jumping from flanking markers [5].
• Using human radiation hybrid mapping and BAC contig construction, we have identified a conserved region of human chromosome 15 homologous to the mesd, nelg, and hsdr1 functional regions [6].
• Genetic interaction between a maternal factor and the zygotic genome controls the intestine length in PRM/Alf mice [7].

Anatomical context of Hsdr1

• Moreover, we could mimic aspects of the alf/hsdr-1 deletion phenotype in vitro by treating primary hepatocyte cultures with an intermediate of tyrosine metabolism [4].
• The "mesoderm-deficient" (msd) and "hepatocyte-specific developmental regulation-1" (hsdr-1) loci, which are proximal and tightly linked to c, are important in the formation of mesoderm and in the regulation of liver- and kidney-specific induction of various enzymes and proteins, respectively [8].

Physical interactions of Hsdr1

• Physical mapping of the albino-deletion complex in the mouse to localize alf/hsdr-1, a locus required for neonatal survival [9].

Other interactions of Hsdr1

• These results indicate that the hsdr-1 locus is dispensable for the glucocorticoid induced transcription of these genes but not of TAT [10].

Analytical, diagnostic and therapeutic context of Hsdr1

• These results unequivocally establish Fah as the gene mapping at alf/hsdr-1 and prove that the phenotype depends ultimately on the blockage of tyrosine metabolism [3].
• Northern blot and in situ hybridization analysis of mouse tissues showed that the cell types that normally express FAH correspond to those that exhibit a phenotype in alf/hsdr-1 deletion mice [4].

References