| First Author | Beechey CV | Year | 1994 |
| Journal | Mouse Genome | Volume | 92 |
| Pages | 353-4 | Mgi Jnum | J:35322 |
| Mgi Id | MGI:82772 | Citation | Beechey CV, et al. (1994) Dosage effects of the distal chromosome 2 imprinting region. Mouse Genome 92:353-4 |
| abstractText | Full text of Mouse Genome contribution: 8. Dosage Effects of the distal chromosome 2 imprinting region. The reciprocal translocation T(2;4)lGo with breakpoints in 2H2 and 4B2 has been utilised to study dosage effects of the distal Chr 2 imprinting region, known to lie between distal band H3 and proximal H4 (Peters et al., Genet. Res. Camb. 1994, in press). Maternal duplication/ paternal deficiency and paternal duplication/maternal deficiency for this region causes different neonatal lethalities with opposite anomalous phenotypes and behaviour (Cattanach & Kirk, Nature 315:496-498, 1985; Cattanach, J. Embryol. Exp. Morphol. 97 Suppl. pp 137-150, 1986). Thus maternal duplication/ paternal deficiency leads to mice with long flat sided bodies with arched backs that become inactive, fail to suckle and die within 24 hours of birth. The reciprocal type, paternal duplication/maternal deficiencies show an effectively opposite phenotype having short square bodies with broad flat backs and are notably hyperkinetic, surviving for several days. TlGo is known to produce viable tertiary trisomics (Beerman et al, Chromosoma 95: 1-7, 1987; Beechey pers. comm.) with a normal chromosome complement plus an extra 4(2) chromosome that encompasses the distal Chr 2 imprinting region. Various matings have been set up with cytogenetic screening of the offspring to see if there are differences amongst tertiary trisomics according to the parental origin of the extra 4(2) chromosome. Initially a male mouse of normal appearance and behaviour was discovered that was a translocation heterozygote combined with tertiary trisomy ie it possesed 3 copies of the distal Chr 2 imprinting region (2, 2(4), 4, 4(2), 4(2).) As the parents of this mouse were both TlGo heterozygotes it was not possible to determine the parental origin of the extra 4(2) chromosome. However, when this male was mated to a normal female a tertiary trisomic daughter was produced that must have inherited the 4(2) chromosome paternally. Thus this female had inherited one maternal and two paternal copies of the Chr 2 distal imprinting region (ie M + 2P) yet appeared normal apart from some dark pigmentation of the external genitalia. When mated to a normal male she produced two litters, these being carefully screened for any evidence of the characteristic phenotypes associated with the distal Chr 2 imprinting region. The first litter consisted of 4 offspring that appeared normal at birth but were missing one day later. The second litter consisted of a single male with an odd head shape, its left eye slightly open, that suckled when fostered to another female. It died a day after birth and a chromosome preparation revealed that it was a tertiary trisomic therefore inheriting the extra 4(2) chromosome from its mother (ie 2M + P). The finding that it suckled was the clearest indication that it did not have the typical phenotype associated with maternal duplication for this region and the reason for its death and unusual head shape remains unknown. Thus in summary, three tertiary trisomics have been produced, none of which had a phenotype usually associated with either maternal or paternal duplication of the distal Chr 2 imprinting region. For two of these the parental origin of distal Chr 2 has been established. One had one maternal and two paternal (M + 2P) copies of the distal Chr 2 imprinting region, was viable to adulthood and of normal appearance and the other had two maternal and one paternal (2M + P) copies of the imprinting region and died soon after birth. The latter did not, however, show the usual characteristics of maternal duplication for this region. Tissues from these mice have been frozen to allow further study when an imprinted gene or genes is discovered in this region of chromosome 2. These findings are preliminary and further outcrosses of TIGo heterozygous males and females to normal mice have been set up with cytogenetic screening of the offspring to produce further tertiary trisomics. The results so far suggest that the phenotype associated with paternal duplication can be rescued by a maternally derived distal Chr 2 and vice versa for a maternal duplication. Furthermore, the failure to recover the typical phenotypes associated with either the maternal or paternal duplication suggests that at least two genes in distal Chr 2 are subject to imprinting, one being paternally imprinted and the other maternally imprinted. Finally, the tertiary trisomic system is a potentially valuable way of investigating other regions subject to imprinting, and may provide a natural rescue for some imprinted phenotypes. Other imprinting regions that could potentially be investigated using this system are proximal Chr 6, distal Chr 12, proximal Chr 17 and distal Chr 17. (Beechey CV & Peters J). |
