Naturally variant autosomal and sex-linked loci determine the severity of iron overload in β2-microglobulin-deficient mice

Hereditary hemochromatosis (HH) is a common chronic human genetic disorder whose hallmark is systemic iron overload. Homozygosity for a mutation in the MHC class I heavy chain paralogue gene HFE has been found to be a primary cause of HH. However, many individuals homozygous for the defective allele of HFE do not develop iron overload, raising the possibility that genetic variation in modifier loci contributes to the HH phenotype. Mice deficient in the product of the β2-microglobulin (β2M) class I light chain fail to express HFE and other MHC class I family proteins, and they have been found to manifest many characteristics of the HH phenotype. To determine whether natural genetic variation plays a role in controlling iron overload, we performed classical genetic analysis of the iron-loading phenotype in β2M-deficient mice in the context of different genetic backgrounds. Strain background was found to be a major determinant in iron loading. Sex played a role that was less than that of strain background but still significant. Resistance and susceptibility to iron overload segregated as complex genetic traits in F1 and back-cross progeny. These results suggest the existence of naturally variant autosomal and Y chromosome-linked modifier loci that, in the context of mice genetically predisposed by virtue of a β2M deficiency, can profoundly influence the severity of iron loading. These results thus provide a genetic explanation for some of the variability of the HH phenotype.

S100B up-regulates macrophage production of IL1β and CCL22 and influences severity of retinal inflammation

Funding: This work was supported by funding awards to Dr Isabel Crane from the National Eye Research Centre, Bristol, UK (Grant ref. SCIAD 058); and NHS Grampian Endowment Trust (Grant ref. 10/16). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Evaluation of an index of biotic integrity : temporal variability and regional application in the midwest /

Mode of access: Internet.

Cumulated list of unclassified index card errata.

"January 1954."

Housing discrimination study : incidence and severity of unfavorable treatment /

"HUD-1327-PDR"--Cover p. 4.

Tri-level study: modification. Task 2: final report on driver/vehicle characteristics related to vehicle condition and causation and an assessment of Indiana PMVI effectiveness to reduce the frequency and severity of accident causes by vehicular-related malfunctions/degradations. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Quantification of smoothness index differences related to Long-Term Pavement Performance equipment type /

"September 2005."

The severity of large truck accidents.

Mode of access: Internet.

Chronological table of and index to the statutes to the end of the session of ...

Twelfth ed. consists of index only.

Design manual of natural methods of cooling electronic equipment; report no. HF-845-D-8. Contract no. NObsr-63043, Bureau of Ships-index no. NE-111611, Sub-task 2.

"Non registered."

List of abbreviations for serial publications used in the fourth series of the Index-catalogue.

Supersedes its Synopsis of style, part 2, 1937.

Tracing Hybrid Collectives of Illness, War, and Medicine in Twentieth- and Twenty-First Century Narratives of Illness

Thesis (Ph.D.)--University of Washington, 2016-06