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

Abstract

Inter-alpha-inhibitor (I alpha I) 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 alpha-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. Mouse poly(A)+ RNAs or endonuclease-restricted mouse DNA were analyzed by standard and pulsed-field gel electrophoresis (PFGE) techniques in agarose gels and blot-hybridized with human H1, H2, H3 or L cDNA probes. The variable sized transcripts and unique restriction fragment patterns detected with each probe indicate that four genes, including one common L gene for A1m and bikunin also exist in mouse. The co-migration of H1- and H3-hybridizing fragments on PFGE suggests that the mouse H1 and H3 genes are also tandemly arranged. An Msp I restriction fragment length polymorphism (RFLP) in the mouse L gene (proposed symbol, Intin-4) links this gene to other genes already mapped at mouse Chr 4 near the brown (b) locus, a homologous region to the human chr 9q32-34 band where the human I alpha I L gene is located. Therefore, a similar number and arrangement of I alpha I genes is found in mouse and human, including the triplication of an H gene ancestor. These results point to an ancient origin of this complex set of genes.

A1M, an extravascular tissue cleaning and housekeeping protein

“…The AMBP gene has been cloned from man [16] and mouse [17], and mapped to a lipocalin gene cluster in the 9q32-33 region in man [16] and to chromosome 4 in mouse [18]. The A1M-exons are separated from the bikunin-exons by a large intron which contains retroposons and other repeated structures, suggesting that it is a recombinatorial hot-spot [17].…”

Irreversible Heavy Chain Transfer to Hyaluronan Oligosaccharides by Tumor Necrosis Factor-stimulated Gene-6

“…TSG-6 transesterifies the HCs to the 6-OH on N-acetylglucosamine in HA. Five different homologous HCs (HC1-5) are present in two gene clusters mapped to different chromosomes (HC1, HC3, and HC4 to chromosome 3, and HC2 and HC5 to chromosome 10) (8). HC4 is unique in that it is not part of I␣I, is not transferred to HA, and is secreted as a free HC species (9,10).…”

Impairment of the Correlation between Urinary Contents of Alpha-1-Microglobulin and Ulinastatin Is Induced by Intracerebroventricularly Administered Interleukin-6 in Mice

“…Mice possess genes for the precursor protein of ·1M and UT, inter-·-trypsin inhibitor and pre-·-trypsin inhibitor, similar to those of humans [13,21], and the relation of urinary contents of ·1M and UT does not differ between the two species (data not shown). In our previous study, we have found that the lack of a positive correlation between urinary contents of ·1M and UT distinguishes Parkinson's disease from other neuropsychiatric diseases such as dementia (Alzheimer-type and vascular dementia), schizophrenia and mood disorder [7], although the mechanism(s) remains to be elucidated.…”

“…In addition, in a gene of the precursor protein of ·1M and UT, an IL-6 sequence motif has been located [12]. Thus, in the present study, we investigated whether or not the relation between urinary contents of ·1M and UT in mice (a species which reportedly possesses a gene similar to that of humans for synthesizing the precursor protein of ·1M and UT) [13] was affected by intracerebroventricularly (i.c.v.) administered IL-1ß or IL-6.…”