High rate of recombination and double crossovers in the mouse pseudoautosomal region during male meiosis.

The recombination rate in meiosis between the mouse X and Y chromosomes was analyzed. Mice heterozygous at two pseudoautosomal alleles, the steroid sulfatase gene and the Mov-15 provirus marker, were crossed. The provirus in the Mov-15 transgenic mouse strain had been previously shown to be carried in the pseudoautosomal region of the sex chromosomes. Recombination frequencies were shown to be 7-fold higher in this region in male meiosis than in female meiosis. Three-point crosses indicated the occurrence in male meiosis of double recombination events in the pseudoautosomal region, with little or no crossover interference, which is in marked contrast to observations made on the similar region of the human sex chromosomes. This result is contrary to a previous model, which predicted a single crossover event in male meiotic pairing of mammalian sex chromosomes

Inactivation and reactivation of sex-linked steroid sulfatase gene in murine cell culture

The murine X-linked steroid sulfatase gene (Sts) normally escapes X inactivation. However, we have observed that most long-term murine cell cultures are deficient in STS activity even though only the L cells are known to be derived from an STS- mouse strain. To investigate this phenomenon, we developed a selective system whereby STS+ cells could be selected from STS- populations. The system is based on making cells dependent on cholesterol-sulfate as the sole source of cholesterol, allowing only STS+ cells to grow. Two STS- cell lines, after treatment with either 5-azacytidine (5AC) or ethyl methane sulfonate (EMS), yielded STS+ revertants, suggesting that their STS- phenotype was due to hypermethylation. To study the evolution of STS- cell lines, we established XO and XX primary lines from STS+ strains; the XX cell line remained STS+ after more than 200 cell doublings whereas the XO became STS- after about 100 doublings. Treatment of this STS- XO cell line with 5AC produced clones with restored STS activity. All the revertants showed a growth disadvantage compared to their STS- counterparts. It would appear that aberrant methylation is the basis for much of the STS deficiency observed in established murine lines and that its propagation is due to the growth advantage of STS- over STS+ cells

The human pseudoautosomal GM-CSF receptor alpha subunit gene is autosomal in mouse

The gene encoding the granulocyte macrophage colony stimulating factor receptor alpha subunit (CSF2RA) has previously been mapped to the pseudoautosomal region of the human sex chromosomes. In contrast, we report that the murine locus, Csf2ra, maps to an autosome in the laboratory mouse. By in situ hybridization and genetic mapping, Csf2ra maps at telomeric band D2 of mouse chromosome 19. This first instance of a pseudoautosomal locus in human being autosomal in mouse, indicates incomplete conservation between the human and mouse X chromosomes and suggests that the genetic content of the pseudoautosomal region may differ between species of eutherian mammals due to chromosomal rearrangements