Mouse albino‐deletions: From genetics to genes in development

Abstract

Six essential genes located near the mouse albino locus have been identified as required during specific periods of development, Amongst these six, each is required either during the preimplantation stages of development, at specific times during gastrulation, within 12 hrs after birth or during juvenile development. These genes were identified as a result of extensive genetic complementation analysis using embryos homozygous for the albino deletions. Although, in principal, the associated developmental abnormalities could result from loss of multiple genes, the deletion phenotype in one case is identical to that induced by chemical mutagenesis. These results indicate that the abnormalities observed in deletion homozygotes may result from single gene loss. The deletions have proven useful not only as genetic tools to localize the position of the genes, but also as molecular entry points to the regions containing these genes. The current methodology being used to isolate candidate genes from the albino region is also reviewed here.

Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos.

“…Approximately 12 loci or genes have been identified, which are required for normal development during gas trulation and before somite formation (E6-E8) (Green 1989;Holdener-Kenny et al 1992). Of these, the pheno type of the recessive lethal mutation t"^^ is most similar to that of HNF-4 homozygotes; t"^^ is one of several em bryonic lethals found in different t haplotypes of the t complex on chromosome 17 (Bennett 1975;Silver 1985).…”

A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse

“…Thus, the T gene product seems to be required to ensure correct formation and/or specification of the mesodermal lineage. Although classical genetic studies have identified a number of spontaneous mutations that similarly interfere with early embryogenesis, the underlying defects have yet to be elucidated at the molecular level (reviewed by Lyon and Searle, 1989;Holdener-Kenny et al, 1992).…”

Rescue of mice homozygous for lethal albino deletions: implications for an animal model for the human liver disease tyrosinemia type 1.

“…Of these, the albino deletion complex on chromosome 7 is perhaps the best characterized phenotypically and molecularly (Rinchik and Russell 1990;Holdener-Kenny et al 1992). Many of the albino deletions cause recessive lethal phenotypes, such as arrest of development at specific embryological stages or failure to survive beyond birth (Erickson et al 1968;Russell et al 1979).…”