Pollard H, Moreau J, Aubourg P
Unité Inserm U29, Hôpital Port-Royal, Paris, France.
J Neurosci Res. 1995 Oct 15;42(3):433-7. doi: 10.1002/jnr.490420318.
Adrenoleukodystrophy (ALD) is a genetic demyelinating disorder caused by the mutation of a gene encoding a 75-kDa peroxisomal protein (ALDP) that belongs to the superfamily of ATP binding casette (ABC) transporters. The PMP 70 gene codes for another peroxisomal ABC transporter that shows 38.5% amino acid identity with ALDP. ALDP and PMP70 have the structure of half transporter and could possibly heterodimerize to form a full transporter within the peroxisomal membrane. Using in situ hybridization histochemistry in rat brain, we demonstrate that ALD and PMP70 mRNAs have different spatial and temporal expression during postnatal development. Whereas expression of PMP 70 mRNA was low at birth and culminates between the 2nd and 3rd week in hippocampus and cerebellum, maximum expression of ALDP was found at birth in all brain areas and decreased thereafter. The absence of coordinated expression of ALD and PMP70 genes suggests therefore that ALD and PMP70 proteins are unlikely to function as exclusive and obligatory partners in the brain.
肾上腺脑白质营养不良(ALD)是一种遗传性脱髓鞘疾病,由编码一种75 kDa过氧化物酶体蛋白(ALDP)的基因突变引起,该蛋白属于ATP结合盒(ABC)转运体超家族。PMP 70基因编码另一种过氧化物酶体ABC转运体,与ALDP的氨基酸同一性为38.5%。ALDP和PMP70具有半转运体结构,可能在过氧化物酶体膜内异源二聚化形成完整的转运体。利用大鼠脑原位杂交组织化学技术,我们证明ALD和PMP70 mRNA在出生后发育过程中具有不同的时空表达。出生时PMP 70 mRNA表达较低,在海马体和小脑的第2至第3周达到峰值,而ALDP在出生时在所有脑区表达最高,此后下降。因此,ALD和PMP70基因缺乏协调表达表明,ALD和PMP70蛋白不太可能在大脑中作为唯一且必不可少的伴侣发挥作用。