The genes for the inter-α-inhibitor family share a homologous organization in human and mouse

Inter-α-inhibitor ( IαI ) and related molecules in human are comprised of three evolutionarily related, heavy (H) chains and one light (L) chain, also termed bikunin. The latter originates from a precursor molecule that is cleaved to yield the bikunin and another protein designated α-1-microglobulin (A1m). The four H and L chains are encoded by four distinct genes designated H1, H2, H3 , and L . The L and H2 genes are localized onto human chromosomes (chr) 9 and 10, respectively, whereas the H1 and H3 genes are tandemly arranged on chr 3.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46989/1/335_2004_Article_BF00355432.pd

Developmental and tissue-specific expression of alpha 1-microglobulin mRNA in the rat

A rat liver cDNA library was constructed in the lambda gt11 expression vector. Three clones expressing alpha 1-microglobulin, an immunosuppressive plasma protein, were detected by screening with rabbit antiserum against rat alpha 1-microglobulin. The alpha 1-microglobulin activity from one of the clones, 6b, was confirmed with monoclonal antibodies in a solid phase radioimmunoassay. The nucleotide sequence of the fragment (165 base pairs) was determined, and the translated amino acid sequence (55 amino acids) showed a 75% homology to human alpha 1-microglobulin (position 122-176). Southern blots of restriction endonuclease-digested rat DNA indicated two distinct genes with alpha 1-microglobulin homology when probed with radioactive cDNA fragment from clone 6b. Northern blots showed the presence of a single mRNA species in rat liver, and the level was low in 1-month-old animals, increased to reach a maximum during adulthood (3 months), and decreased with aging (12 months). The alpha 1-microglobulin concentration in rat serum showed the same age dependence between 1 and 12 months, with the highest values at 3 months. Embryonic development (8.5-day to 17.5-day) was studied using total fetal RNA, and expression of alpha 1-microglobulin mRNA was detected in low amounts only at day 15.5. alpha 1-Microglobulin mRNA levels, studied by an RNA dot blot assay, were high in liver and kidney, low in brain and testis, and none were found in hypothalamus and spleen cells

Derivation of non-lymphopenic BB rats with an intercross breeding

Previous studies have suggested that the development of diabetes in the BB rats does not require the expression of T lymphopenia. In order to derive non-lymphopenic diabetic rats and define the relationship between the T cell abnormalities, MHC genotype, and diabetes, we performed a cross between BB/H and diabetes resistant BB/control followed by an intercross of the F1. In the F2, the overall incidence of diabetes and lymphopenia was 30% and 27%, respectively. Lymphopenia was strongly associated with diabetes (p less than 0.001) and was seen in 76% of the diabetic F2's. However, 6 of the diabetic were non-lymphopenic (24%) and 3 of the non-diabetics were lymphopenic (5%). In the non-lymphopenic diabetic animals, all T cell levels were within the normal range, but diabetes occurred at an earlier age than their lymphopenic littermates (p less than 0.001). In contrast to the strong association between the inheritance of lymphopenia and diabetes, no relationship between diabetes and Class I MHC restriction fragment length polymorphisms was found. We conclude: 1) Diabetes and lymphopenia are strongly associated inherited abnormalities in the BB rat and are not associated with Class I RFLP defined genotypes within the RTIu haplotype, 2) Animals in whom diabetes occurs in the absence of lymphopenia can be derived using this breeding approach 3) In our non-lymphopenic rats, diabetes occurred at an earlier age possibly reflecting the restoration of quantitative or qualitative T cell defects found in lymphopenic BB rats

A deletion in a rat major histocompatibility complex class I gene is linked to the absence of beta 2-microglobulin-containing serum molecules.

Class I major histocompatibility antigens are composed of a heavy chain that is noncovalently associated with beta 2-microglobulin (beta 2m). Most class I molecules are membrane bound, but mouse and rat cDNA clones and genes without a functional code for the transmembrane amino acids have been identified. The membrane-associated class I molecules are important in the control of cell-mediated cytotoxicity, while the function of the soluble molecules remains unclear. Previous studies have shown that beta 2m circulates in rat serum in three different molecular weight classes. The first is free beta 2m (Mr, 12,000), the second is about Mr 70,000, and the third is roughly Mr 200,000. In an inbred subline of immunodeficient, diabetes-prone BioBreeding rats (BioBreeding/Hagedorn), previous work detected two restriction fragment polymorphisms in class I major histocompatibility complex genes, one of them a gene deletion on a 7-kilobase BamHI fragment and the other on a 2-kilobase BamHI fragment. In these rats we have found that the third serum beta 2m-binding size class is absent. Analysis of F1 and F2 individuals following cross-breeding between BioBreeding/Hagedorn rats and genetically related (nondiabetic) control BioBreeding w-subline rats demonstrated that the large-size serum peak of beta 2m was associated with the presence of the class I restriction fragments