e88 Mouse epithelium, serum proteins and urine proteins | Thermo Fisher Scientific (2024)

Nature

Allergens originating from animals are significant components of house and animal laboratory dust (1, 2). Sensitization to animal allergens may occur following direct or indirect contact (3, 4).

Taxonomy

The house mouse, Mus musculus, is the most common mouse living as a commensal of humans (5). Most mice used in laboratories have major contributions from the two species found in Europe, Mus musculus musculus and Mus musculus domesticus (6).

Tissue

Like all rodents, mice have persistent proteinuria (7). When urine in the environment dries, the proteins become airborne on dust particles (8).

The major mouse allergen is a pheromone-binding protein, Mus m 1. Excreted in mouse urine, Mus m 1 is also found on mouse hair follicles and on the skin surface. Allergenic molecules derived primarily from urine, along with those from saliva, are found on hair and epithelial fragments (4, 9).A more minor allergen than Mus m 1, Mus m 2 is a nonurinary allergen that is present on mouse epithelium (3).

The levels of rodent-derived, airborne allergens have been measured and found to be significant, not only in laboratories but also in schools and homes (2, 10).

Worldwide distribution

Native to the Indian subcontinent, the house mouse has now colonized all regions of the world (5). It survives in all climates and may be found indoors and out.

Although mice can be kept as pets, they are normally considered to be pests on account of their ability to establish themselves in buildings such as homes and schools. Their chewing can cause structural damage and their feces and continual dribble of urine lead to contamination (4).

Risk factors

Rodent contact in general has long been identified as a risk factor for IgE sensitization to rodents. The exact nature of the relationship between exposure and the risk of becoming sensitized has been explored in greater depth in recent studies (3).

Laboratory animal workers are at risk of sensitization and up to one-third will have symptomatic asthma (4). An atopic background and the intensity of exposure are further risk factors (4).

The National Cooperative Inner-City Asthma Study demonstrated that an increase of Mouse skin test sensitivity was associated with a Mus m 1 level of greater than 1.6 µg/g (11).

One study investigating the relationship between exposure and risk of IgE sensitization showed that prevalence rates of skin test sensitivity to mouse in a population of suburban children increased as exposure to mouse allergens in bedroom dust increased (12).

In an inner-city population with mouse allergens 100- to 1000-fold higher than those in the suburban population, an increasing risk of sensitization throughout the first three quartiles of exposure was demonstrated. At the highest levels of exposure, however, sensitization was attenuated, suggesting that at very high levels of exposure, some measure of protection may be conveyed (3).

Among inner-city children with asthma, allergen exposure, a history of atopy, and sensitization to co*ckroach allergen have been shown to be significant risk factors for mouse sensitization (11).

Pediatric issues

The School Inner-City Asthma Study demonstrated that, not only are mouse allergens the most commonly detected allergen in schools, but levels are significantly higher than in homes (13).

Living environment

Exposure to mouse allergen in the home is widespread. Studies have shown detectable mouse allergen in three-quarters of US homes. In suburban Maryland homes, the figure is almost as high, at nearly 70% (10), while, in some inner-city communities, almost all homes have detectable mouse allergen – levels are around 100-fold higher than in suburban homes (3, 14).

In kitchens of US homes in general, the median detectable Mus m 1 level is 0.36 μg/g. The median is much lower in suburban Maryland homes, at 0.007 μg/g. Strikingly, in kitchens of inner-city homes, the median Mus m 1 level ranges from 1.6 to 24.1 μg/g (3).

Several studies have identified predictors of detectable mouse allergen, for example, the presence of exposed food remains in the kitchen or visible evidence of mice. Poor housing conditions, such as living in poverty or multifamily dwellings, older or poorly maintained buildings that have holes or cracks in walls and doors, and co*ckroach infestation are all associated with detectable levels of mouse allergen (3, 11, 14).

Worldwide distribution

House mice are a ubiquitous commensal of humans and may be found colonizing all types of building. Being small and agile, they can fit into very small spaces, and can gain entry to buildings through the smallest gaps. In search of food, they infest animal housing, such as pig and poultry units, grain stores, warehouses, hospitals and shops. While wild mice feed primarily on vegetable matter, commensal mice will eat any accessible human or animal food and also non-food material, such as soap (5).

Allergy to mice is a significant occupational health problem, particularly because of the large numbers of mice used in laboratories (3).

Main

Early studies examining mouse allergen exposure in occupational settings sampled airborne particles and analyzed their size distribution and density in the environment. Mouse allergen is carried predominantly on particles measuring less than 10 μm. At this size, particles may be easily deposited in airways (3).

Environmental source

In occupational settings, mouse ‘load’, a function of mouse density and room ventilation, has been shown to be directly related to higher airborne mouse allergen levels (3).

In a home setting, it is generally not possible for the clinician to obtain settled dust samples. However, collection of a history, including reports of recent mouse sightings, can be a strong predictor of higher levels of mouse allergen exposure. In one study, parent reports of having seen mice had a 90% positive predictive value for mouse allergen levels greater than 0.5 μg/g. The absence of mouse sightings, however, cannot be relied upon to rule out clinically relevant mouse exposure (3).

Main methods

Vacuum pumps are used to collect samples by drawing air through a filter. The captured airborne particles are analyzed for Mus m 1 content (3).

Measures

Mus m 1 exposure is expressed as mass per volume of air, normally using units ng/m³. It is derived from a known flow rate of the sampling pump (in liters per minute) and duration of sampling time (in minutes) (3).

Asthma

In occupational settings, the association between laboratory animal allergy or occupational asthma and rodent exposure is well documented. Symptoms may include rhinoconjunctivitis, eczema, urticaria, and asthma. Cases are often identified using disease surveillance methods, and exposure reduction may be achieved by the use of respiratory protection or by reassignment to a job where exposure is minimized. Medication may also be required (3).

It is estimated that between 11% and 44% of people working with laboratory animals will develop allergies related to their occupation. Of those, between 4% and 33% will go on to develop occupational asthma or other lower airway symptoms (3, 4).

The clinical relevance of mouse allergen exposure and sensitization outside of the laboratory setting has also been demonstrated. Exposure to mouse allergen has been associated with a diagnosis of asthma in adult populations. Furthermore, mouse allergen sensitization has been associated with more severe asthma in women. Sensitization to mouse allergen alone has been shown to be a risk factor for young children with allergic airway disease. A birth cohort study in New York City showed that mouse allergen-sensitized, two- to three-year-old children were at greater risk than were non-sensitized children, of developing rhinitis, wheeze and eczema (3).

Worse asthma outcomes have been associated with the combination of mouse sensitization with exposure, as opposed to just exposure or sensitization alone. Two recent studies measured morbidity in mouse-sensitized inner-city children who were exposed to high levels of mouse allergen. One-quarter of children in a Baltimore City preschool population demonstrated evidence of IgE sensitization to mouse. Bedroom settled dust samples were analyzed and those children exposed to greater than 0.5 µg/g mouse allergen had more symptomatic days, cough without a cold, exercise-related symptoms and use of short-acting ß-agonists, than either children who were non-sensitized or those who were exposed to lower exposure levels. Risk of hospitalization was greatly increased, while risk of an unscheduled physician or emergency department visit for asthma also increased two- to threefold in the sensitized and exposed children, compared with the less-exposed or non-sensitized children (3).

Allergic rhinitis

In occupational settings, the association between laboratory animal allergy or occupational asthma and rodent exposure is well documented. It is estimated that between 11% and 44% of people working with laboratory animals will develop allergies related to their occupation. Symptoms may include rhinoconjunctivitis, eczema, urticaria, and asthma. Cases are often identified using disease surveillance methods, and exposure reduction may be achieved by the use of respiratory protection or by reassignment to a job where exposure is minimized. Medication may also be required (3).

The clinical relevance of mouse allergen exposure and sensitization outside of the laboratory setting has also been demonstrated (3, 7). Sensitization to mouse allergen alone has been shown to be a risk factor for young children with allergic airway disease. A birth cohort study in New York City showed that mouse allergen-sensitized, two- to three-year-old children were at greater risk than were non-sensitized children, of developing rhinitis, wheeze and eczema (3).

Atopic dermatitis

In occupational settings, the association between laboratory animal allergy or occupational asthma and rodent exposure is well documented. It is estimated that between 11% and 44% of people working with laboratory animals will develop allergies related to their occupation. Symptoms may include rhinoconjunctivitis, eczema, urticaria, and asthma. Cases are often identified using disease surveillance methods, and exposure reduction may be achieved by the use of respiratory protection or by reassignment to a job where exposure is minimized. Medication may also be required (3).

Sensitization to mouse allergen alone has been shown to be a risk factor for young children with allergic airway disease. A birth cohort study in New York City showed that mouse allergen-sensitized, two- to three-year-old children were at greater risk than were non-sensitized children, of developing rhinitis, wheeze and eczema (3).

Prevention strategies

For asthma patients demonstrating evidence of IgE sensitization of mouse, environmental interventions that will reduce mouse allergen levels in the home should be recommended. Integrated pest management involves using multiple strategies that will reduce food sources for mice, eliminate them from the home, and prevent them from regaining access. Examples of such strategies include clearing away exposed food and storing foods in containers through which mice cannot chew, setting traps and repairing structural damage, such as cracks and holes, in the home. One pilot study demonstrated a 75% reduction in mouse allergen levels in the home (3).

Allergenic molecules

A number of mouse allergens have been characterized to date. The allergens vary in concentration in the urine, serum, and pelts of mice (11, 16). Mus m 1 is a 19kDa lipocalin odorant-binding protein found in hair, dander, and urine (7). Mus m 1 is a major allergen and a prealbumin. Formerly known as MUP (mouse urinary protein) and also known as MA1 and Ag 1 (7, 15), Mus m 1 is produced by liver cells, circulates in the bloodstream and is excreted by the kidneys. Production of Mus m 1 is testosterone dependent, thus, levels in the serum and urine of male mice are approximately four times higher than in female mice (7, 16).

Mus m 2 is a 16kDa glycoprotein found in hair and dander (7, 16).

Albumin is a relatively larger protein, and is found in serum and urine (3). In mouse-sensitized individuals, approximately 30% are sensitized to this allergen (7, 16).

Since serum proteins are excreted in urine, they will constitute a proportion of the significant levels of airborne rodent allergens found in laboratories, homes, and schools (7, 17).

Included within MUPs are a number of Mus m 1 isoforms, along with other closely related proteins (8). Mus m 1 is the only mouse allergen listed on the WHO/IUIS Allergen Nomenclature Database, and just two isoforms are described (18). However, additional isoforms do exist (8). It is not yet known whether, in addition to Mus m 1, there are other important mouse allergens. For example, studies have demonstrated the allergenic potential of mouse serum albumin (8).

Different mouse allergen extracts, urine, serum proteins and, to a lesser and more variable degree, epithelial extract, all contain Mus m 1 (8). Epithelial extract and mouse urine have been shown previously to be of equal diagnostic value (8). However, an investigation into the T cell response to epithelial extract versus mouse urine has shown that two clinical phenotypes, asthmatic and rhinitic patients, demonstrate slightly different responses to these two allergen sources (8).

With this taken into account, testing patients against all three allergen extracts could increase the chance of identifying mouse sensitization (19).

Cross-reactivity

Practically all respiratory allergens originating from animals, including mouse, belong to the lipocalin family of proteins. The major allergens of horse, cow, dog, mouse and co*ckroach are all examples of these, along with beta-lactoglobulin, from cow’s milk (15). Thus, there may be a certain degree of cross-reactivity.

The major rat allergen is Rat n 1. Excreted in the urine, Rat n 1 is also a lipocalin and a pheromone-binding protein. Rat n 1 shares 60-80% hom*ology with Mus m 1, which means that in most, if not all, rodent-sensitized patients, rat and mouse sensitization is coexistent (3, 20).

Author:RubyDuke Communications

Reviewer: Dr. Christian Fischer

Last reviewed: January 2021