A novel selection algorithm for maximizing genetic response while constraining the rate of inbreeding is presented. It is shown that the proposed method controls the rate of inbreeding by maintaining the sum of squared genetic contributions at a constant value and represents an improvement on previous procedures. To maintain a constant rate of inbreeding the contributions from all generations are weighted equally and this is facilitated by modifying the numerator relationship matrix. By considering the optimization of the contributions of many generations the initial mating proportions (the genetic contributions to the next generation) are not equal to their long-term values, but are set equal to the expected long-term contributions given the current information. This is confirmed by the regression of the long-term contributions on the assigned mating proportions being close to one. The gain obtained from the selection algorithm is compared with the maximum theoretical genetic gain under constrained inbreeding. It is concluded that this theoretical upper bound is in general unattainable, but from this a concept of genetic efficiency in terms of resources and constraints is derived.

The murine Xce locus, first identified by Bruce Cattanach, infiuences the primary choice of the X chromosome to be inactivated. Methylation of a GC-rich region (DXPas34) that includes multiple 34 bp repeats and lies some 15 kb 3′ to Xist has been shown to vary with Xce haplotype. The degree of methylation on the active X chromosome at this locus represents one of the few molecular correlates of Xce action currently available. Data relating to the specificity and other characteristics of this association are presented.

Tetraploid (4n) cells do not contribute equally to all tissues of midgestation mouse chimaeras and mosaics. Our previous studies of early blastocysts showed that 4n cells are preferentially allocated to the mural trophectoderm of the early blastocyst and this may contribute to the restricted distribution pattern seen at later stages. In this study of later-stage blastocysts we found evidence for selection against 4n cells. The contribution of 4n cells to 4n[harr ]2n chimaeric blastocysts decreased between E3·5 and E4·5 days, whereas the composition of 2n[harr ]2n controls changed little over this period. These results suggest that, prior to implantation, blastocysts have already lost some tetraploid cells from their embryonic and extra-embryonic lineages due to a combination of preferential allocation of 4n cells to the mural trophectoderm and selection against 4n cells throughout the embryo.

The identification of novel mutants and their genetic and phenotypic characterization leads initially to fairly well-defined areas of experimentation. However, some mutant models lend themselves to investigations in fields that at first glance may appear remote from the original observation.

This has been true of the hypogonadal (hpg) mouse first discovered by Bruce Cattanach (Cattanach et al., 1977). In these mutant mice there is a failure of postnatal gonadal development such that paired testicular weight in 60-d-old hpg males is less than 10 mg whilst in normal littermates the testes weigh nearly 200 mg. The seminal vesicles of the mutants are extremely atrophic, indicating a failure of androgen production by the testes. In female mutants ovarian follicles rarely advance beyond the pre-antral stage and the uterus is thin and thread-like.

Genomic imprinting is an epigenetic mode of gene regulation that results in expression of the autosomal ‘imprinted’ genes from only a single allele, determined exclusively by parental origin. To date over 20 imprinted genes have been identified in mouse and man and these appear to lie in clusters in restricted regions on a subset of chromosomes. This may be a critical feature of imprinting suggesting a domain-type mode of regulation. Imprinted domains are replicated asynchronously, show sex-specific meiotic recombination frequencies and have CpG-rich regions that are differentially methylated, often associated with the imprinted genes themselves. Mouse distal chromosome 7 is one such domain, containing at least nine imprinted genes spanning over 1 Mb of DNA. For the maternally expressed p57Kip2 gene, passage through the female germline is essential to generate the active state, whereas passage through the male germline is needed to force the maternally expressed H19 gene into an inactive state. It is therefore possible that the mouse distal chromosome 7 imprinted domain is actually composed of two or more independently regulated subdomains.

This review concerns the general problem of understanding growth control in the whole organism, starting with a saltatory change in size generated by a chromosome translocation or a mutation in a single gene. In particular, changes in insulin-like growth factor-II levels, by genetic and embryological manipulation, have major effects on wet weight size, but the intermediary events that link these levels to this measure of growth are uncertain. Thus it is currently impossible to eliminate any of the intermediary candidate processes that have been observed in model systems, including changed rates of apoptosis, cell multiplication, protein synthesis, capillary permeability and fluid transport.

Previous studies have shown that the distal region on mouse chromosome (Chr) 2 is subject to imprinting as mice with maternal duplication/paternal deficiency (MatDp.dist2) and the reciprocal (PatDp.dist2) for this region exhibit phenotypic anomalies at birth and die neonatally. We show here that imprinting effects are detectable in utero. Notably PatDp.dist2 embryos show an increase in wet weight compared with normal, which peaks at 16·5 d post coitum (dpc), and diminishes by birth, whereas the wet weight of placenta is slightly reduced in the latter half of gestation. Newborns have increased length of the long bones. By contrast, the wet weight of MatDp.dist2 embryos decreases during the second half of gestation. Measurements of dry weights of embryos at 16·5 dpc have indicated that there is no difference in either PatDp.dist2 or MatDp.dist2 compared with normal so that the wet weight differences are due to fluid retention in PatDp.dist2 but fluid loss in MatDp.dist2. In PatDp.dist2 embryos excess fluid is particularly prominent in the subcuticular skin layer, whereas by birth fluid is evident around the neck and tongue. At 16·5 dpc the PatDp.dist2 embryos are severely oedematous, as the average fluid content per unit dry weight per embryo was increased by 40%, whereas the MatDp.dist2 embryos are dehydrated as the average water content per unit dry weight per embryo was reduced by 6%. A preliminary conclusion is that there is neither growth enhancement in PatDp.dist2 nor growth retardation in MatDp.dist2 offspring.