MouseCyc: a curated biochemical pathways database for the laboratory mouse

Abstract

Linking biochemical genetic data to the reference genome for the laboratory mouse is important for comparative physiology and for developing mouse models of human biology and disease. We describe here a new database of curated metabolic pathways for the laboratory mouse called MouseCyc http://mousecyc.jax.org. MouseCyc has been integrated with genetic and genomic data for the laboratory mouse available from the Mouse Genome Informatics database and with pathway data from other organisms, including human.

Figure 1

Mouse arginine degradation III (arginine decarboxylase/agmatinase) pathway. The enzyme has been biochemically identified in rats [26], but the identities of the mammalian arginine decarboxylase genes remain elusive.

Figure 2

Oxidative ethanol degradation pathway in the mouse. (a) Initial PathoLogic prediction assigned six enzymes to EC 1.1.1.1, five enzymes for EC 1.2.1.3 and one enzyme for EC 6.2.1.13 reactions. (b) Manually resolved pathway for Mus musculus. The association of Adh6b with EC 1.1.1.1 was removed because, while no functional studies of ADH6B enzyme have been reported yet, the protein lacks Phe140, a strictly conserved residue in ethanol-active enzymes [32]. For EC 1.2.1.3, the list of genes was updated with only those aldehyde dehydrogenase superfamily members that have experimental evidence of involvement in ethanol metabolism. Finally, the last reaction in this pathway is EC 6.2.1.1, rather than EC 6.2.1.13, which is implicated in lipid biosynthesis. This posted correction to the MetaCyc database was propagated to the MouseCyc pathway using the PathoLogic incremental update tool. (c) The MouseCyc server permits direct comparison of a mouse biochemical pathway with the same pathway from an external PGDB, HumanCyc [19].

Figure 3

Linking the MGI and MouseCyc databases. (a) Details of the MGI entry for the galactose-1-phosphate uridyl transferase (Galt) gene now include the list of biochemical pathways (shown in bold) associated with this gene. (b) Graphical representation of the Leloir pathway and the position of the GALT enzyme within it. (c) MouseCyc entry for the GALT enzyme, showing the description of the disease associated with the human ortholog of the mouse GALT enzyme.

Figure 4

An OmicsViewer representation of the metabolic pathways in MouseCyc. Reactions catalyzed by enzymes with targeted (knockout) mutation or gene trap alleles in the corresponding genes are shown in color: red depicts existence of both knockout and gene trap alleles; blue indicates knockout alleles; green indicates gene trap alleles. The graphic was generated by processing the Phenotypic Allele report from the MGI FTP site. The data of interest were converted to a two column tab-delimited file with current MGI symbols for genes in the first column and a numeric value in the second column. The numeric value indicated if a gene had a targeted allele, gene trapped allele, or both. Each value corresponded to a specific color among the range of colors supported by the OmicsViewer. The data used to generate this figure are available at [42].

Figure 5

Examples of prominent biochemical pathways identified in mouse oocytes. (a) The protein citrullination pathway has recently been shown to be essential for early development, as targeted mutation of Padi6 renders females infertile [44]. Note that Padi6 is the only gene of the peptidyl arginine deiminase family expressed in oocytes. (b) The inability of glucose utilization by mouse oocytes may be due to the lack of hexokinases required for the first step in glycolysis. Genes next to the corresponding reactions are shown in black (expressed in the oocytes) or in grey (not expressed).