Disease relevance of Psmb9

• Allelic polymorphism of the Lmp-2 gene may be involved in peptide selection, leading to autoimmune disease susceptibility [1].
• The Lmp-2 sequence from a non-obese diabetic (NOD) mouse, a model animal for autoimmune diabetes, was compared with that from a Balb/c mouse [2].

High impact information on Psmb9

• We have developed a strategy to detect, quantify, and map NCRs in parallel to CRs, at the Psmb9 meiotic recombination hot spot, in male and female mouse germ lines [3].
• The Lmp-2 and Lmp-7 gene products are two subunits of the large cytosolic proteasome complex possibly involved in generation of endogenous peptides [1].
• To study the genetic polymorphism of the Lmp-2 gene, we used a published cDNA sequence as a consensus sequence and PCR-amplified, cloned, and sequenced the Lmp-2 gene from 12 inbred mouse strains [1].
• Molecular basis of genetic polymorphism in major histocompatibility complex-linked proteasome gene (Lmp-2) [1].
• We found three amino acid variants, LMP-2d, LMP-2b, and LMP-2q, which partially correlated with restriction fragment length polymorphism variants identified with Southern blots [1].

Biological context of Psmb9

• Reduced expression of Tap1 and Lmp2 antigen-processing genes in the nonobese diabetic (NOD) mouse due to a mutation in their shared bidirectional promoter [4].
• Observed altered substrate specificity of Lmp2 containing proteasomes isolated from NOD mice was consistent with reduced Lmp2 activity [4].
• Northern blot revealed reduced amounts of Tap1 and Lmp2 mRNA in NOD mice, and 5'-rapid amplification of cDNA ends revealed the loss of a transcription start site of Lmp2 in these animals [4].
• We have determined the nucleotide sequence of the region encompassing the whole Lmp-2 gene and three exons of Tap-1, which spans 8 kb in the mouse genome [2].
• The mouse Lmp-2 gene is located within the major histocompatibility complex (MHC) class II region and encodes a subunit of the 20S cytosolic proteasome [5].

Anatomical context of Psmb9

• Lmp2 and Tap1 are genes located in the MHC class II region, and they encode proteins participating in the generation and transport of endogenous peptides for T cell education [4].
• In murine bone marrow-derived macrophages, LPS and TNF-alpha induced Tap1 and up-regulated Lmp2, which is constitutively expressed at low levels [6].
• Northern analysis of Lmp2, Lmp7, and Lmp10 showed expression in heart, liver, thymus, lung, and spleen, but not in brain, kidney, skeletal muscle, or testis [7].

Other interactions of Psmb9

• By making deletions of the promoter, we determined that only the proximal GAS box is required for LPS induction of Tap1 and Lmp2 [6].
• These data suggest that NOD proteasome dysfunction is due to a tissue- and developmental-stage-specific defect in expression of the MHC-linked Lmp2 gene, resulting in altered transcription factor NF-kappaB activity, and that this defect contributes to pathogenesis in NOD mice [8].
• Twenty-three breakpoints were confined within 5.4 kb in the Lmp-2 hotspot, and six breakpoints from the cas4 cross were located in the Pb hotspot, which we have now confined to a 15 kb segment [9].
• Sequence analysis of the mouse gene encoding DELTA, designated Lmp19, indicates that it consists of six exons and five introns, similar to the Lmp2 gene [10].

References