Molecular mapping of albino deletions associated with early embryonic lethality in the mouse

Niswander, Lee; Kelsey, Gavin; Schedl, Andreas; Ruppert, Siegfried; Sharan, Shyam K.; Holdener-Kenny, Bernadette; Rinchik, Eugene M.; Edström, J.-E.; Magnuson, Terry

doi:10.1016/0888-7543(91)90234-6

Cited by 27 publications

(6 citation statements)

References 13 publications

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“…Efforts by several groups to clone the alf/hsdr-1 gene focused on utilizing the different overlapping albino deletions to narrow down the location of the gene (Niswander et al 1991;Kelsey et al 1992}. In 1992, two groups successfully isolated the Fah gene from the 310-kb region of overlap between different deletions, thereby raising the question whether loss of Fah was the cause for the alf/hsdr-1 deletion phenotype Ruppert et al 1992).…”

Section: The Fah Gene Is a Candidate For The Alf/hsdr-1 Locusmentioning

confidence: 99%

“…This observation has led to the hypothesis that a regulatory liver gene [hepatocyte-specific developmental regulation locus (hsdr-1)] is localized within the deletion (McKnight et al 1989). This locus has also been termed Detailed mapping of the deletion interval in the c 14c°s mice has identified a 310-kb fragment within which the alf/hsdr-1 gene must be localized (Niswander et al 1991;Kelsey et al 1992). Recently, two groups reported the isolation of a liver-specific eDNA from the 310-kb deletion interval encoding fumarylacetoacetate (FAA) hydrolase (Fah, EC 3.7.1.2) Ruppert et al 1992).…”

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confidence: 99%

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Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice.

Grompe

Al‐Dhalimy

Finegold

et al. 1993

Genes & Development

335

297

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Mice homozygous for the c 14c°s albino deletion die as neonates as a result of liver dysfunction. Previous mapping studies have associated this defect with a 310-kb fragment encoding the hepatocyte-specific developmental regulation locus (alf/hsdr-1). The gene encoding fumarylacetoacetate hydrolase (Fah), a metabolic enzyme that catalyzes the last step of tyrosine catabolism, also maps to the same deletion interval. To test whether the neonatal defects found in the albino deletion mutants are attributable to loss of Fah, and not to another gene mapping to the deletion, we have generated Fah mutant mice by gene targeting in embryonic stem cells. Fah-deficient mice die within 12 hr after birth from hypoglycemia and liver dysfunction. In addition, the same pattern of altered liver mRNA expression found in the albino deletion mutants was also found in affected animals. We conclude that the neonatal lethal and liver dysfunction phenotype of the alf/hsdr-1 deletion is entirely attributable to loss of Fah.

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Section: The Fah Gene Is a Candidate For The Alf/hsdr-1 Locusmentioning

confidence: 99%

mentioning

confidence: 99%

Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice.

Grompe

Al‐Dhalimy

Finegold

et al. 1993

Genes & Development

335

297

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“…I . D7CwllDand D7Cw2D are genomie loci defined by cloned deletion-breakpoint-fusion fragments(53). The distal side of the deletion chromosomes arc shown as dark lines below the genetic map.…”

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confidence: 99%

Mouse albino‐deletions: From genetics to genes in development

1992

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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.

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“…Several approaches can be used to identify gene products that are differentially expressed between the germ layers and to evaluate stage dependence of expression of particular genes. One approach exploits developmental mutants to define relevant genetic loci (Herrman et al, 1990;Conlon et al, 1991;Niswander et al, 1991;Radice et al, 1991). Immunofluorescence and immunocytochemical analyses of tissue sections reveal differentially expressed protein and carbohydrate epitopes (Dziadek and Adamson, 1978;Fenderson et al, 1988;Muramatsu, 1988;Senior et al, 1988;Ezzell et al, 1989;Schaart et al, 1989;Slager et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of protein synthesis in mouse embryos. II: Differentiation of endoderm, mesoderm, and ectoderm

Latham

Beddington

Solter

et al. 1993

Molecular Reproduction Devel

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The changes in protein synthesis that occur during differentiation of the primitive germ layers were examined by high-resolution, two-dimensional gel electrophoresis of proteins synthesized in 6.5 and 7.5 days postcoitum (d.p.c.) mouse embryos. For 6.5 d.p.c. embryos, protein synthesis patterns were compared between whole extraembryonic and embryonic regions and between embryonic visceral endoderm and embryonic ectoderm. For 7.5 d.p.c. embryos, comparisons were made between extraembryonic and embryonic regions and between isolated embryonic endoderm, mesoderm, and ectoderm. Each of the isolated 7.5 d.p.c. germ layers was divided into anterior and posterior fragments in order to evaluate possible regional differences in gene expression along the anterior-posterior axis. Comparisons of protein synthesis patterns revealed the greatest difference between isolated endoderm and ectoderm, indicating that by as early as 6.5 d.p.c. patterns of gene expression differ significantly between these tissues. The greatest similarities were found between ectoderm and whole embryonic regions and between endoderm and whole extraembryonic regions, which most likely reflects the overall cellular compositions of the embryonic and extraembryonic regions. Based on their patterns of synthesis, four groups of proteins were identified that were preferentially synthesized in either endoderm or ectoderm. These provide useful markers for studying differentiation in these tissues. One other protein, migrating at the position expected for vimentin, was synthesized at an elevated rate in isolated mesoderm. We also observed differences in rates of synthesis of alpha-tubulin and tropomyosin-5 indicative of potential differences in cytoskeletal composition among the germ layers beyond those previously described. The difference in overall protein synthesis patterns between anterior and posterior regions was greatest in the embryonic endoderm, indicating that differentiation along the anterior-posterior axis may be initiated sooner or may proceed more rapidly in the endoderm than in the other germ layers. These data provide the first quantitative evaluation of the degree to which differentiation of the three primitive germ layers affects protein synthesis patterns and reveal potentially useful markers of endoderm and ectoderm differentiation.

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Molecular mapping of albino deletions associated with early embryonic lethality in the mouse

Cited by 27 publications

References 13 publications

Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice.

Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice.

Mouse albino‐deletions: From genetics to genes in development

Quantitative analysis of protein synthesis in mouse embryos. II: Differentiation of endoderm, mesoderm, and ectoderm

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