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The expression of Huntingtin‐associated protein (HAP1) mRNA in developing, adult and ageing rat CNS: implications for Huntington's disease neuropathology
Author(s) -
Page Keith J.,
Potter Laurence,
Aronni Silvia,
Everitt Barry J.,
Dunnett Stephen B.
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00185.x
Subject(s) - stria terminalis , neocortex , biology , in situ hybridization , globus pallidus , huntingtin , hypothalamus , amygdala , endocrinology , messenger rna , neuropathology , putamen , subiculum , medicine , basal ganglia , central nervous system , neuroscience , huntington's disease , dentate gyrus , genetics , disease , gene
Using radioactive in situ hybridization, we have mapped the expression of Huntingtin‐associated protein (HAP1) mRNA in rat brain at developmental stages (E12–E19, P0–P21), in adult rats (3 months) and in ‘aged’ (19–21 months) rats. Using two pairs of 45mer oligonucleotide probes specific for HAP1A and a probe which recognizes regions of both the HAP1A and HAP1B mRNA sequences (panHAP1), we find that the expression of HAP1 mRNA is specific to the CNS and restricted predominantly to anatomically connected limbic structures, particularly the amygdala (medial and corticomedial nuclei), the hypothalamus (arcuate, preoptic, paraventricular and lateral hypothalamic area), bed nucleus of the stria terminalis (BNST) and the lateral septal nuclei. HAP1 mRNA was detected in embryos at E12 and displayed a prevalent distribution in the developing limbic structures by E15. In aged, 19–21‐months‐old, rats there is a downregulation of HAP1 mRNA expression across all CNS loci where HAP1 was previously abundant. The lowest levels of HAP1 mRNA expression corresponded with the areas of greatest pathological cell loss in Huntington's disease (HD); the caudate putamen, globus pallidus and neocortex. These observations support the suggestion that HAP1 plays an important role in the neuropathology of HD.