PubMed Health⌕ Search

Biomedical subjects

J de Moes

Publications and source records attributed to J de Moes.

4 recordsLinked to original sources

Defective spectrin integrity and neonatal thrombosis in the first mouse model for severe hereditary elliptocytosis.

Mutations affecting the conversion of spectrin dimers to tetramers result in hereditary elliptocytosis (HE), whereas a deficiency of human erythroid alpha- or beta-spectrin results in hereditary spherocytosis (HS). All spontaneous mutant mice with cytoskeletal deficiencies of spectrin reported to date have HS. Here, the first spontaneous mouse mutant, sph(Dem)/ sph(Dem), with severe HE is described. The sph(Dem) mutation is the insertion of an intracisternal A particle element in intron 10 of the erythroid alpha-spectrin gene. This causes exon skipping, the in-frame deletion of 46 amino acids from repeat 5 of alpha-spectrin and alters spectrin dimer/tetramer stability and osmotic fragility. The disease is more severe in sph(Dem)/sph(Dem) neonates than in alpha-spectrin-deficient mice with HS. Thrombosis and infarction are not, as in the HS mice, limited to adults but occur soon after birth. Genetic background differences that exist between HE and HS mice are suspect, along with red blood cell morphology differences, as modifiers of thrombosis timing. sph(Dem)/sph(Dem) mice provide a unique model for analyzing spectrin dimer- to-tetramer conversion and identifying factors that influence thrombosis.

Age Factors↗

Localization of a gene for expression of mouse mammary tumor virus antigens in the GR/Mtv-2- mouse strain.

The GR/Mtv-2- mouse strain is congenic to the GR strain but lacks the Mtv-2 gene for high amounts of mouse mammary tumor virus (MMTV) virion particles in the milk and early mammary tumors. With a sensitive competition radioimmunoassay for individual viral proteins of MMTV, substantial amounts of the gag proteins p27 and p10 could still be detected in extracts of the mammary glands of GR/Mtv-2- mice, but essentially no viral envelope antigens. The genetic transmission of the MMTV gag expression in the GR/Mtv-2- strain was investigated. In a cross with the virus-negative BALB/c strain, the MMTV p27 expression behaved as a dominant feature. Double backcross analysis proved that the p27 expression was governed by a single gene located on chromosome 11, cloe to the Es-3 locus. The gene was thereby not allelic to any of the previously described MMTV induction genes, Mtv-1 and Mtv-2, and is therefore called Mtv-3. It is concluded that the total MMTV expression in the GR strain is under control of two separate loci, Mtv-2 on chromosome 18, inducing high levels of complete virus particles and also early mammary tumors; and Mtv-3 on chromosome 11, coding for partial MMTV expression.

Animals↗

Development of a congeneic line of the GR mouse strain without early mammary tumours.

Based on the previous observation that Mtv-2 controls the appearance of pregnancy-dependent mammary tumours and the early expression of mammary tumour virus (MTV)-antigens in the milk, an attempt was made to develop a congeneic GR line, without this locus, by introducing genetic material of the C57BL/10 strain. The cross-intercross system was used for this purpose. The mice of the even-numbered generations were selected for the absence of the Mtv-2 locus with the early maammary tumour (EMT) test and during the later cycles with the immunodiffusion (ID) test for MTV-antigens in the milk. After six cycles of cross-intercross, brother-sister mating was started with mice selected for the absence of Mtv-2. After two brother-sister matings the milk-transmitted MTV was eliminated by foster-nursing. Of the foster-nursed subline 233 mice (16 of the first, 118 of the second and 99 of the third generation) were tested for the presence of Mtv-2 with one or two of the following three methods: (1) ID-test, (2) EMT-test and (3) by examination of the development of spontaneous mammary tumours in breeding females. The tests were negative in 226 mice. This indicates that Mtv-2 was absent in nearly all mice of the congeneic subline. The positive reactions in the seven other tested mice were weaker than that observed in the GR strain and in GR mice foster-nursed by BALB/c. The presence of the Mtv-2 gene in the seven positive mice of the congeneic line is doubtful. With the ID test, viral antigens were detectable in 50% of the milk samples from the first lactation period of mice of the segregating backcross I population [GR congeneic X (GR congeneic X GR)], indicating a one-gene difference between the congeneic GR line and the progenitor GR strain.

Animals↗