Lorenz B, Francis F, Gempel K, Böddrich A, Josten M, Schmahl W, Schmidt J, Lehrach H, Meitinger T, Strom T M
Abteilung Medizinische Genetik, Kinderpoliklinik, Ludwig-Maximilians-Universität, Goethestr. 29, 80336 München, Germany.
Hum Mol Genet. 1998 Mar;7(3):541-7. doi: 10.1093/hmg/7.3.541.
Two mouse mutations gyro (Gy) and hypophosphatemia (Hyp) are mouse models for X-linked hypophosphatemic rickets and have been shown to be deleted for the 5' and 3' end of the mouse homolog of PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome; formerly called PEX), respectively. In addition to the metabolic disorder observed in Hyp mice, male Gy mice are sterile and show circling behavior and reduced viability. The human SMS (spermine synthase) gene maps approximately 39 kb upstream of PHEX and is transcribed in the same direction. To elucidate the complex phenotype of Gy mice, we characterized the genomic region upstream of Phex. By establishing the genomic structure of mouse Sms, a 160-190 kb deletion was shown in Gy mice, which includes both Phex and Sms. There are several pseudogenes of SMS / Sms in man and mouse. Northern analysis revealed three different Sms transcripts which are absent in Gy mice. Measurement of polyamine levels revealed a marked decrease in spermine in liver and pancreas of affected male Gy mice. Analysis of brain tissue revealed no gross or histological abnormalities. Gy provides a mouse model for a defect in the polyamine pathway, which is known to play a key role in cell proliferation.
两种小鼠突变体，即回旋（Gy）和低磷血症（Hyp），是X连锁低磷性佝偻病的小鼠模型，并且已分别显示在与X染色体上的内肽酶具有同源性的磷酸盐调节基因（PHEX，以前称为PEX）的小鼠同源物的5'和3'末端缺失。除了在Hyp小鼠中观察到的代谢紊乱外，雄性Gy小鼠不育，表现出转圈行为且活力降低。人类精胺合酶（SMS）基因定位于PHEX上游约39 kb处，并以相同方向转录。为了阐明Gy小鼠的复杂表型，我们对Phex上游的基因组区域进行了表征。通过建立小鼠Sms的基因组结构，发现Gy小鼠存在160 - 190 kb的缺失，其中包括Phex和Sms。人和小鼠中存在几种SMS / Sms假基因。Northern分析揭示了三种不同的Sms转录本，在Gy小鼠中不存在。多胺水平测量显示，受影响的雄性Gy小鼠肝脏和胰腺中的精胺显著减少。脑组织分析未发现明显的大体或组织学异常。Gy为多胺途径缺陷提供了一个小鼠模型，已知多胺途径在细胞增殖中起关键作用。
