Meyer R A, Henley C M, Meyer M H, Morgan P L, McDonald A G, Mills C, Price D K
Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA.
Genomics. 1998 Mar 15;48(3):289-95. doi: 10.1006/geno.1997.5169.
Gy, along with Hyp, is a dominant mutation of the normal gene Pex causing X-linked hypophosphatemia in the mouse. Hemizygous Gy male mice, however, have greater defects in survival, bodily growth, skeletal mineralization, and neurological function than those found in heterozygous Gy females or in Hyp mice. Since the gene for spermine synthase is immediately upstream of the homologous human gene PEX, we compared the effects of the Gy and Hyp mutations on both the spermine synthase gene and the Pex gene. Barely detectable levels of spermine (< 5% of normal) with elevated levels of its precursor, spermidine, were found in organs of Gy male mice compared to normal male littermates. Neither Gy females nor Hyp male mice were significantly affected. Four missing introns of the spermine synthase gene were identified in Gy male mice, suggesting extensive gene disruption. A pseudogene for spermine synthase was also identified in the mouse genome. Pex mRNA was found in several but not all tissues studied in adult normal mice. Pex mRNA was altered in both Gy and Hyp mice. All male Hyp mice were lacking the 3' end of the Pex message, whereas all male Gy mice were deficient at the 5' end. In summary, the Gy mutation is associated with a recessively expressed mutation of the spermine synthase gene, leading to spermine deficiency, and a dominantly expressed mutation of the Pex gene, leading to hypophosphatemia. Alterations in two contiguous genes in Gy may explain the additional phenotypic abnormalities present in the Gy male mouse.
Gy与Hyp一样，是正常基因Pex的显性突变，可导致小鼠X连锁低磷血症。然而，半合子Gy雄性小鼠在生存、身体生长、骨骼矿化和神经功能方面的缺陷比杂合子Gy雌性小鼠或Hyp小鼠更为严重。由于精胺合酶基因紧邻同源人类基因PEX的上游，我们比较了Gy和Hyp突变对精胺合酶基因和Pex基因的影响。与正常雄性同窝小鼠相比，在Gy雄性小鼠的器官中发现精胺水平几乎检测不到（<正常水平的5%），而其前体亚精胺水平升高。Gy雌性小鼠和Hyp雄性小鼠均未受到显著影响。在Gy雄性小鼠中鉴定出精胺合酶基因的四个缺失内含子，提示存在广泛的基因破坏。在小鼠基因组中还鉴定出一个精胺合酶假基因。在成年正常小鼠研究的多个但并非所有组织中都发现了Pex mRNA。Pex mRNA在Gy和Hyp小鼠中均发生了改变。所有雄性Hyp小鼠均缺失Pex信息的3'末端，而所有雄性Gy小鼠在5'末端存在缺陷。总之，Gy突变与精胺合酶基因的隐性表达突变相关，导致精胺缺乏，以及Pex基因的显性表达突变，导致低磷血症。Gy中两个相邻基因的改变可能解释了Gy雄性小鼠中出现的额外表型异常。
