Presence of NAD pyrophosphorylase in skeletal muscle in dystrophic mice

Summary NAD pyrophosphorylase (ATP:NMN adenylyltransferase) activity has been measured in the skeletal muscle of dystrophic mice. The amount of this enzyme in the dystrophic mice, as determined by three different methods, was about one half of that in the controls. In addition, the concentration of ATP was too low to be detected in crude extracts of dystrophic mouse skeletal muscle, which were prepared using Tris buffer alone or Tris buffer containing either 3 M KCl, or 1 mM PMSF.     

A study on the pharmacokinetics in mouse of adenine-9-beta-D-arabinofuranoside 5-monophosphate conjugated with lactosaminated albumin

In plasma of mice injected with adenine-9-beta-D-arabinofuranoside monophosphate (ara-AMP) coupled to human lactosaminated serum albumin (L-HSA) some of the ara-AMP molecules are enzymatically released, whereas others remain linked to L-HSA. Evidence has been obtained that ara-AMP is not deaminated when it is conjugated to L-HSA, in contrast to the free drug which is rapidly metabolized to its hypoxanthine derivative.     

HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions.

Cancer predisposition in hereditary non-polyposis colon cancer (HNPCC) is caused by defects in DNA mismatch repair (MMR). Mismatch recognition is attributed to two heterodimeric protein complexes: MutSalpha (refs 2, 3, 4, 5), a dimer of MutS homologues MSH2 and MSH6; and MutSbeta (refs 2,7), a dimer of MSH2 and MSH3. These complexes have specific and redundant mismatch recognition capacity. Whereas MSH2 deficiency ablates the activity of both dimers, causing strong cancer predisposition in mice and men, loss of MSH3 or MSH6 (also known as GTBP) function causes a partial MMR defect. This may explain the rarity of MSH6 and absence of MSH3 germline mutations in HNPCC families. To test this, we have inactivated the mouse genes Msh3 (formerly Rep3 ) and Msh6 (formerly Gtmbp). Msh6-deficient mice were prone to cancer; most animals developed lymphomas or epithelial tumours originating from the skin and uterus but only rarely from the intestine. Msh3 deficiency did not cause cancer predisposition, but in an Msh6 -deficient background, loss of Msh3 accelerated intestinal tumorigenesis. Lymphomagenesis was not affected. Furthermore, mismatch-directed anti-recombination and sensitivity to methylating agents required Msh2 and Msh6, but not Msh3. Thus, loss of MMR functions specific to Msh2/Msh6 is sufficient for lymphoma development in mice, whereas predisposition to intestinal cancer requires loss of function of both Msh2/Msh6 and Msh2/Msh3.     

Cytogenetic and biochemical comparison of Mus musculus and Mus hortulanus

Two chromosome markers of Mus hortulanus are described: a dotted Y chromosome exceeding half of the length of autosome 19, and the 'domesticus' type of C-banding in the X chromosome. In Mus musculus from distant regions of the USSR (more than 200 specimens of various subspecies), the Y chromosome is equal to autosome 19, and the X chromosome is of the 'molossinus' type. Specific biochemical characteristics of house mice of the USSR are shown.     

The effect of moderate hemodilution with fluosol-DA or normal saline on acetaminophen disposition in the rat

Hemodilution with 40 ml/kg of Fluosol or saline reduced the acetaminophen Vd and the acetaminophen sulfate ClM at 48 or 72 h, respectively. Fluosol hemodilution increased the acetaminophen renal excretion at 24 and 72 h. But at 48 h, Fluosol hemodilution either inhibited the renal secretion of acetaminophen or enhanced its reabsorption.     

A combination of a particular HLA-DP beta allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease

Coeliac disease is an autoimmune disease of the intestinal mucosa, elicited by ingestion of wheat gluten in genetically susceptible individuals. Susceptibility to coeliac disease has been associated with the serologically defined variants DR3 and DR7 of the class II antigens encoded by the HLA-D region. Three related class II antigens, each consisting of an alpha and a beta glycoprotein chain, have been identified and are designated HLA-DR, HLA-DQ, and HLA-DP. These highly polymorphic transmembrane proteins bind peptides derived from the processing of foreign antigens and present them to T lymphocytes; they also influence the specificity of the mature T-cell repertoire. The role of HLA-DP polymorphism in susceptibility has not been as fully explored as that of the other class II antigens because of the complexity of the primed lymphocyte typing (PLT) method for determining DPw specificities. Here we use a new DNA-based method of HLA-DP typing to analyse the distribution of DP beta alleles in a group of coeliac disease patients and healthy controls. Two specific DP beta alleles (DPB4.2 and DPB3) are increased in the patient population. Comparison of the DP beta sequences suggests that the polymorphic residues at position 69 and at 56 and 57 may be critical in conferring susceptibility. Further, the contribution of the susceptible DP beta alleles appears to be independent of linkage to the previously reported DR3 and DR7 markers for coeliac disease. The distribution of DQ alpha and beta alleles in patients suggests that a specific DQ heterodimer may be responsible for the observed DR associations. Individuals with both this DQ antigen and a specific DP beta allele are at increased risk for coeliac disease.