X-linked anaemia of mice: An hereditary disorder of iron absorption

Pinkerton, Peter H (1969) X-linked anaemia of mice: An hereditary disorder of iron absorption. MD thesis, University of Glasgow.

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Abstract

The X-linked anaemia of mice (gone symbol, sla) is hypoehroxato and microcytic in character. Typically, the mean corpuscular haemoglobin concentration, the mean cell volume and the mean cell diameter are reduced. Anaemia is moderately severe in young hemizygous male and homozygous female mice, and regresses spontaneously with age. Heterozygous female animals show little or no haematological abnormality, and duality of the red cell population is not seen. The iron stores of anaemic mice, as determined both chemically and histochemically, are depleted at all ages. The clearance of iron from the plasma le rapid and the appearance of radio-iron in the red cells, after parenteral injection, is both greater and more rapid than normal. The serum iron concentration is low and the total serum iron binding capacity is elevated, as is the free erythrocyte protoporphyrin concentration. The anaemia responds well to parenteral iron dextran. Together, these findings are characteristic of iron deficiency. In contrast to the usual situation in iron deficiency in man and other mammals, intestinal iron absorption is not increased in X-linked anaemia of mice; indeed a significantly-low level of absorption of inorganic iron at three dose levels (0.1, 1.0 and 10 mug) has been found. Histo-chemical studies reveal abnormal accumulation of stainable iron in the mucosal epithelium of the small bowel of anaemic and heterozygous mice. These findings imply that the deficiency of iron is a consequence of malabsorption of iron by the small bowel, probably as a result of a primary, genetically controlled, fault in the metabolic processes of iron transfer from the mucosa cell to the plasma. The histochomical findings in the mucosa epithelium of heterozygous carriers are consistent with, although they do not constitute proof of the provisions of the Lyon hypothesis of X-chromosome inactivation. X-linked mouse anaemia does not, at present, seem to be a model for any known form of heritable human anaemia, but is potentially a useful tool in the investigation of the still mysterious processes whereby iron is transferred from the mucosal epithelium to the plasma. A hypothetical model explaining known features of iron absorption, and incorporating possible sites of action of the sla gene, is presented and discussed. It is postulated that the sla gene controls the production either of an enzyme ("iron transferase") necessary for the transfer of iron to the plasma from the mucosal epithelial cell of the small bowel, or of a carrier substance ("cytoferrin") to which iron must be bound for this transfer to be achieved.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Genetics
Date of Award: 1969
Depositing User: Enlighten Team
Unique ID: glathesis:1969-72739
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06
URI: http://theses.gla.ac.uk/id/eprint/72739

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