Mouse serum proteins

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Code: e76
Latin name: Mus spp.
Source material: Serum
Family: Muridae
Common names: Mouse, House mouse, Common house mouse
The white Mice used in research laboratories are albinos bred from Mus musculus.

Mus domesticus is the most common Mouse that is a commensal of man. But in the familes Muridae and Cricetidae are many wild species of Mouse, and rarer commensals such as the Doormouse.
 
Direct or indirect contact with animal allergens frequently causes sensitisation.
 
Animal allergens are major components of house and animal laboratory dust.

Allergen Exposure

Geographical distribution
Native to Asia, House Mice are now ubiquitous. They exist in all climates and are routinely found both indoors and out. Their constant gnawing damages buildings, furniture and equipment. Mice carry diseases such as salmonella and leptospirosis. They are everyday pests because of their consumption of foodstuffs, and also because their continual dribble of urine and their feces cause contamination. Mice breed more prolifically than Rats, and spread faster, being smaller (which makes concealment easier) and more migratory, but are more easily controlled by poison, traps and predators. They are generally not as troublesome as Rats. In cultivated fields they may be beneficial, eating weed seeds and insects.
 
Environment
Agile and having a varied diet, Mice are found in every kind of building. They are a particular problem in poultry units, Pig housing, grain stores, warehouses, shops, and hospitals. They often migrate from cultivated fields into buildings after harvest. Where conditions permit, Mice may be found in meadows, along watercourses, and in other places where vegetation is dense enough to afford concealment, but they are not nearly as common in undisturbed or natural habitats.
 
Especially because of the numbers of Mice used in laboratories, allergy to Mice is an important occupational health problem.
 
Unexpected exposure
Like Rats, Mice interact unseen with humans, through mainly nocturnal foraging, which leaves behind urine, feces, saliva and skin flakes on many surfaces, especially those used for the preparation of food.
 
Allergens
Mouse allergens were identified over 2 decades ago. Major allergens were found in Mouse skin, serum, and urine: a 67 kDa protein, identical to Mouse albumin, and an approx. 17 kDa protein. Some individuals were sensitised predominantly to the large allergen, some to the smaller allergen, and one group of patients reacted to both allergens (1) .
 
The concentration of the major allergens from Mouse, including Mouse serum albumin (MSA) and Mouse urinary protein (MUP) complex, vary in urine, serum, and pelts of Mice (2) .
 
To date, a number of serum allergens have been characterised.
 
Mus m 1 is a major allergen and a prealbumin. This 19 kDa protein is found in hair, dander and urine. This allergen is a lipocalin-odorant binding protein (3, 4) and was formerly known as MUP (major urinary protein) and also known as MAI and Ag1 (5-11). Mus m 1 is produced in liver cells, circulates in the bloodstream, and is cleared by the kidneys. Males produce approximately 4 times more of this allergen than females. The allergen is low in serum (6, 12).
 
Albumin, a 65-69 kDa protein, is found in serum and urine. Approximately 30% of Mouse sensitised individuals are sensitised to this allergen (13).
 
Serum proteins, being present in urine, will be present in the significant concentrations of airborne rodent allergens that have been measured in both laboratories and apartments in inner cities (14-16).
 
Mouse allergens are carried mainly on particles of 6-18 microns. Allergen levels have been shown to correlate well with the number of animals present in the room and the degree of worker activity during sampling (17).  The higher the number of animals in a room, the higher the allergen concentrations, and higher concentrations were also associated with cleaning activities. The highest personal exposure levels occurred when contaminated bedding and high numbers of conscious animals were handled. The highest airborne Mouse allergen levels have been reported to occur during manual emptying of cages, during changing of cages on an unventilated table and during handling of male animals on an unventilated table (18, 19). The proportion of time spent on these tasks determined the degree of allergen exposure to a large extent.
 
A study reported that total Mus m 1 recovered ranged from 0.2 to 1.5 ng/m3 in rooms without Mice and 0.5 to 15.1 ng/m3 in rooms with Mice. Allergen recovered from the zone of worker activity ranged from 1.2 to 2.7 ng/m3 in rooms without Mice and from 16.6 to 563.0 ng/m3 in rooms with Mice. Direct Mouse contact was associated with the highest levels of exposure to Mus m I. Analysis revealed the bulk of allergen to be in mid-particle size range (3.3 to 10 microns) for Mouse-containing rooms and in small particle size range (0.43 to 3.3 microns) for non-Mouse-containing rooms, suggesting that small particles were carried along corridors from rooms with Mice into non-Mouse-containing rooms (20).
 
In disturbed air, allergen concentration has been shown to increase between 1.4-fold, for albumin allergens, and 5-fold, for crude allergens. The proportion of small particles increased from 1.4% in calm air to 4.5% in disturbed air (21).
 
The concentration and type of Mouse allergen varies between locations and within the same location. Mouse pelt extract allergenic activity may be detected in rooms away from Mouse-care rooms, whereas Mouse urine allergenic activity may be found only in the Mouse-care room. In a study, airborne allergen content ranged from 1.8 to 825 ng/m3 and varied according to both the number of Mice and the amount of work activity in the rooms (2).
 
Mouse allergens are also very prevalent in ordinary homes. Of inner-city homes in Baltimore and Cleveland, USA, 95% had detectable Mouse allergen (Mus m 1) in at least one room, with the highest levels found in kitchens (kitchen: range, 0-618 microg/g; median, 1.60 microg/g; bedroom: range, 0-294 microg/g; median, 0.52 microg/g; television-living room: range, 0-203 microg/g; median, 0. 57 microg/g). By city, 100% of the kitchens in Baltimore had detectable Mouse allergen, with a lower percentage (74%) in Cleveland. Mouse allergen levels correlated according to room. Furthermore, 49% of the homes had reported problems with Mice within the previous year, and 29% of the homes had evidence of Mice in one or more rooms on home inspection; these homes had higher levels of Mouse allergen. Higher allergen levels were also associated with evidence of cockroach infestation in any room (22).

Potential Cross-Reactivity

In IgE immunoblot inhibition studies and histamine release tests, it has been demonstrated that patients who react to Dog albumin exhibit IgE reactivity with purified albumins from Cat, Mouse, Chicken, and Rat. Significant sequence homologies have been demonstrated with albumins from different species: Human: 82.6%, Pig: 81.8%, Cattle: 77.3%, Sheep: 78.8%, Mouse: 75.8%, and Rat: 76.2% (23).
 
Practically all respiratory animal allergens, including Mouse, characterised at the molecular level belong to the lipocalin family of proteins. Examples are the major allergens of Horse, Cow, Dog, Mouse and Cockroach as well as beta-lactoglobulin of Cow's milk (4). A certain degree of cross-reactivity is thus possible.

Clinical Experience

IgE mediated reactions
Mouse allergens found in dust, urine, epithelium and saliva are a frequent cause of asthma, allergic rhinitis and allergic conjunctivitis, mainly in laboratory workers but also in ordinary individuals (2, 24-26).
 
Various studies have examined the prevalence of allergic disease in the work place to Mouse. Initial studies reported that about 20% of the exposed workers have symptoms of allergy to Mice (27). In a study evaluating the risk of laboratory animal allergy among research staff working in laboratories separate from the animal confinement area, 20% of the subjects had serum specific IgE >0.35 kU/l to Rat urinary allergens and/or Mouse urinary allergens, and 32% had experienced animal work-related symptoms, although 90% of aeroallergen samples from the laboratories in question were below the detection limit. More than 4 years of exposure significantly increased laboratory animal sensitisation and symptoms. Working mainly with male rodents resulted in increased risk for sensitisation and for symptoms (28).
 
Hollander et. al. demonstrated that the prevalence rates of allergy symptoms caused by working with Rats and Mice were 19% and 10%, respectively (29). A large epidemiological study of 5000 laboratory workers reported symptoms in 26% exposed to Mice, 25% to Rats, 31% to Guinea Pigs, 30% to Rabbits, 26% to Hamsters, 25% to Dogs, 30% to Cats and 24% to Monkeys (30). Allergic rhinoconjunctivitis with nasal congestion, rhinorrhoea, sneezing and itchy, watery eyes can occur in up to 80% of symptomatic workers (9).
 
Although Mouse allergen is known to cause occupational asthma in laboratory workers, its potential significance in home environments has been underplayed. Through skin-specific IgE tests, 89 (18%) of 499 inner-city children were shown to be sensitised to Mouse. Children whose homes had Mouse allergen levels above 1.60 microg/g in the kitchen had a significantly higher rate of Mouse sensitisation than those with levels below (23% vs 11%). Atopy was also significantly related to Mouse sensitisation, with 40% of those with more than 4 positive skin-specific IgE responses having Mouse sensitivity, compared with 4% of those with no other positive skin-specific IgE responses (31).
 
Two hundred and sixty-three United Arab Emirates nationals with a respiratory disease suspected of being of allergic origin were submitted to skin- and serum-specific IgE measurement. Of these individuals, 8.3% were sensitised to Cat fur, 4.9% to Goat hair, and 0.7% to Rat hair and Mouse hair (32).
 
Importantly, children of parents exposed to Mice, Rats and Hamsters in an occupational setting, e.g., a laboratory, were shown to be more likely to have allergic symptoms, and to have significantly more positive skin-prick tests against allergens from the hair of laboratory animals, compared to children of non-exposed parents (33).
 
See also: Mouse e88, Mouse epithelium e71, and Mouse urine proteins e72.
 
Compiled by Dr Harris Steinman, harris@zingsolutions.com

References

  1. Siraganian RP, Sandberg AL. Characterization of mouse allergens. J Allergy Clin Immunol 1979;63(6):435-42
  2. Twiggs JT, Agarwal MK, Dahlberg MJ, Yunginger JW. Immunochemical measurement of airborne mouse allergens in a laboratory animal facility. J Allergy Clin Immunol 1982;69(6):522-6
  3. Robertson DHL, Cox KA, Gaskell SJ, Evershed RP, Benyon RJ. Molecular heterogeneity in the major mouse urinary proteins on the house mouse Mus musculus. Biochem J 1996;316:265-272
  4. Mantyjarvi R, Rautiainen J, Virtanen T. Lipocalins as allergens. Biochim Biophys Acta 2000;1482(1-2):308-17
  5. Schumacher MJ. Characterization of allergens from urine and pelts of laboratory mice. Mol Immunol 1980;17:1087-95
  6. Lorusso JR, Moffat S, Ohman JL. Immunologic and biochemical properties of the major mouse urinary allergen (Mus m 1). J Allergy Clin Immunol 1986;78:928-37
  7. McDonald, B., M. C. Kuo, J. L. Ohman, and L. J. Rosenwasser. A 29 amino acid peptide derived from rat alpha 2 euglobulin triggers murine allergen specific human T cells (abst). J Allergy Clin Immunol 1988;83:251
  8. Clarke, A. J., P. M. Cissold, R. A. Shawi, P. Beattie, and J. Bishop. Structure of mouse urinary protein genes: differential splicing configurations in the 3'-non-coding region. EMBO J 1984;3:1045-1052
  9. Bush RK, Wood RA, Eggleston PA. Laboratory animal allergy. J Allergy Clin Immunol 1998;102(1):99-112
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  12. Finlayson JS, Asofsky R, Potter M, Runner CC. Major urinary protein complex of normal mice: origin. Science 1965;149:981-2
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  14. Swanson MC, Agarwwal MK, Reed CE. An immunochemical approach to indoor aeroallergen quantitation with a new volumetric air sampler: studies with mite, roach, cat, mouse and guinea pig antigens. J Allergy Clin Immunol 1985;76:724-9
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  18. Thulin H, Bjorkdahl M, Karlsson AS, Renstrom A. Reduction of exposure to laboratory animal allergens in a research laboratory. Ann Occup Hyg 2002;46(1):61-8
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  21. Sakaguchi M, Inouye S, Miyazawa H, Kamimura H, Kimura M, Yamazaki S. Particle size of airborne mouse crude and defined allergens. Lab Anim Sci 1989;39(3):234-6
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  23. Spitzauer S, Schweiger C, Sperr WR, Pandjaitan B, Valent P, Muhl S, Ebner C, Scheiner O, Kraft D, Rumpold H, et al. Molecular characterization of dog albumin as a cross-reactive allergen. J Allergy Clin Immunol 1994;93(3):614-27
  24. Vojta PJ, Friedman W, Marker DA, Clickner R, Rogers JW, Viet SM, Muilenberg ML, Thorne PS, Arbes SJ Jr, Zeldin DC. First National Survey of Lead and Allergens in Housing: survey design and methods for the allergen and endotoxin components. Environ Health Perspect 2002;110(5):527-32
  25. Huang JL, Wang SY, Lin KL, Hsieh KH. Mouse dander-allergic bronchial asthma--a case report. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi 1991;24(2):248-54
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  29. Hollander A, Gordon S, Renstrom A, Thissen J, Doekes G, Larsson PH, et al. Comparison of methods to assess airborne rat and mouse allergen levels. I. Analysis of air samples. Allergy 1999;54(2):142-9
  30. Aoyama K, Ueda A, Manda F, Matsushita T, Ueda T, Yamauchi C. Allergy to laboratory animals: an epidemiological study. Br J Ind Med 1992;49(1):41-7
  31. Phipatanakul W, Eggleston PA, Wright EC, Wood RA; National Coooperative Inner-City Asthma Study. Mouse allergen. II. The relationship of mouse allergen exposure to mouse sensitization and asthma morbidity in inner-city children with asthma. J Allergy Clin Immunol 2000;106(6):1075-80
  32. Lestringant GG, Bener A, Frossard PM, Abdulkhalik S, Bouix G. A clinical study of airborne allergens in the United Arab Emirates. Allerg Immunol (Paris) 1999;31(8):263-7
  33. Krakowiak A, Szulc B, Gorski P. Allergy to laboratory animals in children of parents occupationally exposed to mice, rats and hamsters. Eur Respir J 1999;14(2):

 

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.