Disease relevance of Spnb1

• Blood parameters and histopathology of the jaundiced mouse were compared with that from spherocytic mice, which have a hemolytic anemia caused by deficiency of erythroid alpha-spectrin, yet can survive the postnatal period transfusion free [1].
• Thrombosis and secondary hemochromatosis play major roles in the pathogenesis of jaundiced and spherocytic mice, murine models for hereditary spherocytosis [1].
• The adult jaundiced and spherocytic mice present with greatly decreased hematocrit and red blood cell counts, reticulocytosis, and bilirubinemia, leading secondarily to hepatosplenomegaly and cardiomegaly [1].
• The ja/ja and normal newborn mice were injected intravenously with a total of 8.7 x 10(6) genetically marked +/+ marrow cells/g body weight [2].
• The presence of circulating cytokines was discussed in the context of the postoperative complications observed in jaundiced patients [3].

High impact information on Spnb1

• The severe deficiency of spectrin in the red blood cells of ja/ja mice is the result of a beta spectrin defect [4].
• Unconjugated bilirubin (UCB) causes encephalopathy in severely jaundiced neonates by damaging astrocytes and neurons [5].
• The genetic data confirm that the point mutation is responsible for the severe reductions in beta-spectrin mRNA of jaundiced mice [6].
• The murine mutation jaundiced is caused by replacement of an arginine with a stop codon in the mRNA encoding the ninth repeat of beta-spectrin [6].
• The erythroid alpha-spectrin gene is tightly linked to the spherocytosis locus on chromosome 1 and the jaundiced locus is on chromosome 12, tightly linked to the erythroid beta-spectrin gene [7].

Biological context of Spnb1

• The peak LOD score was obtained with a marker for Spnb1 encoding erythroid beta-spectrin, an obvious candidate gene [8].
• Complete nucleotide sequence of the murine erythroid beta-spectrin cDNA and tissue-specific expression in normal and jaundiced mice [9].
• Transfection of the FLAG epitope tagged wild-type beta I sigma 2 or Providence beta I sigma 2 cDNA constructs into C2C12 myoblasts demonstrated by sedimentation velocity analysis that spectrin beta I sigma 2 Providence formed alpha II/-beta I sigma 2 heterodimers in muscle cells but not heterotetramers [10].
• The recipient acquired the blood phenotype of the primary ja/ja host [2].
• The treatment significantly increased red cell counts and extended the average lifespan to 5 months beyond that previously reported for ja/ja mice transfused at birth [2].

Anatomical context of Spnb1

• Steady state levels of the mutant transcripts are reduced when hybridized with a probe to repeats 2 through 6 with the exception of the 7.2-kb transcript that is unique to heart and skeletal muscle tissues, and is present at normal and elevated levels, respectively, in ja/ja mice [9].
• As a prerequisite for determining the molecular defect of the jaundiced mutation, we have cloned and sequenced the complete murine reticulocyte cDNA for normal Spnb-1 [9].
• Myofibers of mutant mice lacking beta-spectrin (ja/ja) have a more uniform distribution of both the alpha1 and alpha2 subunits of the Na,K-ATPase in the sarcolemma, supporting the idea that the rectilinear sarcomeric pattern assumed by the Na,K-ATPase in wild-type muscle requires beta-spectrin [11].
• The results indicate donor stem cells (a) prolong life in the jaundiced mice, but (b) do not survive long-term when injected into newborn mice [2].
• The presence of an activated state of macrophages in jaundiced mice was concluded from the observed high spontaneous cytokine release and significantly higher release after stimulation (p less than 0.05) [3].

Associations of Spnb1 with chemical compounds

• Adult mutant mice are not jaundiced and bilirubin levels do not differ from normal mice [12].
• Injections of sulfonamide further increased average synaptic delays in jaundiced rats [13].
• RESULTS: Compared with sham-operated mice, jaundiced mice showed significantly higher levels of malondialdehyde and lower concentrations of reduced glutathione in the liver [14].

Other interactions of Spnb1

• After 12 days, substantial interleukin-6 levels were observed in jaundiced mice (100 pg/ml), whereas levels in sham mice further decreased (p less than 0.001) [3].
• From 23-42 degrees C, the dystrophin constructs also appear less temperature-sensitive in unfolding compared to a well-studied betaI-spectrin construct [15].
• Studies on a cerebellar 50,000-dalton protein associated with cerebellar hypoplasia in jaundiced Gunn rats: its identity with glial fibrillary acidic protein as evidenced by the improved immunoblotting method [16].

Analytical, diagnostic and therapeutic context of Spnb1

• Allelism tests indicate that it is not allelic with known hemolytic anemia mutants in mice [hemolytic anemia (sphha), jaundiced (ja), normoblastic anemia (nb), and spherocytosis (sph and sph2Be)] [12].
• Nonablated ja/ja neonates simultaneously transfused and given intravenous injections of normal marrow become chimeric for donor cells [17].
• Green light may be more efficient and safer than shorter wavelength exposure when treating jaundiced newborns with phototherapy [18].

References