The Y* rearrangement in mice: new insights into a perplexing PAR

Abstract

In essence, the Y* rearrangement in the mouse is a Y chromosome that has been hijacked by a non-Y centromere attached distal to the pseudoautosomal region (PAR). All the Y-unique material is thought to be unaltered, but the recombinatory behaviour of the Y* with the X during male meioisis led to the conclusion that part of the PAR is inverted. In the course of a cross set up to introduce the X-linked mutation Patchy fur (Paf) into XY* males, the Y* chromosome was found to carry the wild type allele of Paf. Paf maps close to the X PAR boundary, so we hypothesised that the inverted region of the Y* PAR originated from an X chromosome that provided not only an inverted copy of proximal PAR, but also an X PAR boundary together with some adjacent X-unique material that included the Paf locus. This hypothesis was validated by Southern analysis using an X PAR boundary probe to show that Y* has an X PAR boundary. Thus the Y* PAR has resulted from an end to end fusion of an X and a Y PAR. Furthermore, it was shown that in conjuction with this PAR-PAR fusion, there has been deletion of both copies of the distally located pseudoautosomal gene Steroid sulfatase (Sts).

Sex chromosome complement affects social interactions in mice

“…When the p53 mice were crossed with the FCG, XX individuals of both sexes were more likely to die in utero than XY − individuals . To ask if the presence of two X chromosomes was involved in neural tube-related lethality a second study used the XY* mouse to generate offspring (these are very close to an XO genotype; Burgoyne et al, 1998;Eicher et al, 1991). The XX individuals were the most likely to have neural tube deficits, suggesting that the X genes that escape inactivation may increase the risk of this developmental disorder.…”

An analysis of meiotic impairment and of sex chromosome associations throughout meiosis in XYY mice

“…Indeed, in spontaneously occurring XYY males, where the two Y's are necessarily homologous and where Y-Y synapsis may be extensive (Palmer et al, 1990;Tease, 1990), the second chiasma could be so proximal that some "radial" trivalents will resolve into chain trivalents at diakinesis/MI. Conversely, in XYY* X trivalents, where the Y* X lacks a non-PAR Y axis (Burgoyne et al, 1998), the formation of a second chiasma will be inhibited, thus accounting for the very low incidence with which a second chiasma forms (Rodriguez and Burgoyne, 2000).…”

Evidence that sex chromosome asynapsis, rather than excess Y gene dosage, is responsible for the meiotic impairment of XYY mice

“…The initial cross used to generate the XYY* X males for the production cross was between an XY* X female (on an MF1 random bred background) and a 129 male, so that the XYY* X sons carried a 129 Y chromosome, an MF1 X chromosome, and a Y* X chromosome on an MF1 × 129 F 1 genetic background. The Y* X chromosome comprises the PAR and an X PAR boundary, together with adjacent X-chromosome material and a non-Y centromere Burgoyne et al, 1998). These XYY* X males were then crossed to XXY -females on an MF1 background.…”

“…These animals are sterile owing to an almost total spermatogenic block at the first meiotic metaphase stage (MI) (Kot and Handel, 1990;Sutcliffe et al, 1991); any sperm that are produced are grossly abnormal and frequently diploid (Levy and Burgoyne, 1986). However, when an Y* X chromosome, comprising a pseudoautosomal region (PAR) attached to a non-Y centromere, lacking any Y-specific DNA Burgoyne et al, 1998) was provided as a synaptic partner for the XSxr a chromosome, the meiotic block was overcome (Burgoyne et al, 1992). This provided clear evidence for a meiotic checkpoint that monitors sex chromosome synapsis (or some consequence thereof).…”