http://vet.sagepub.com/Veterinary Pathology Online

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 DOI: 10.1177/0300985811429810

2012 49: 4Vet PatholR. S. Sellers and J. M. Ward

Toward a Better Understanding of Mouse Models of Disease  

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Editorial

Toward a Better Understanding ofMouse Models of Disease

The use of genetically engineered mice in biomedical

research is extensive and has led to notable advances in the

understanding of disease pathogeneses; in fact, the National

Medal of Science was awarded this year to Dr Ralph Brinster,

VMD, PhD, for his contributions in this field. Veterinarians

have been and continue to be on the forefront of evaluating

genetically engineered mice. However, the histopathological

interpretation of findings in these modified mice is deceptively

intricate.

Many pathologists wonder what is so difficult about

phenotyping genetically engineered mice: all you have to do

is look at enough mutant and control mice and note the histo-

logical differences. If only it were that simple! Even in the best

of circumstances—appropriate numbers of mutant mice with

only 1 gene mutation and the littermate controls—interpreting

the findings can be daunting in part because of unanticipated

effects (eg, leaky promoters, neomorphic or hypomorphic alle-

lic expression instead of allelic deletion, microbial infections)

and genetic dissimilarity between ES cells and the backcross-

ing strains. The variation in background lesions and responses

to infectious agents or genetic manipulation between inbred

laboratory mouse strains can be extensive; the complexity of

the genetic variation between inbred strains of mice cannot

be underestimated.

Unfortunately, training in mouse histology, histopathology,

and physiology relative to strain variation, normal background

findings, sexual dimorphisms, aging lesions, and embryonic

development in typical pathology residency programs has not

kept pace with the use of genetically engineered mice in

research. As pathologists, we rely on images of both normal

and abnormal tissues to expand our ability to recognize patterns

and interpret findings. Pathologists who work with mice, par-

ticularly genetically engineered mice, learn extensively by

experience and word of mouth as well as by scattered mouse

pathology texts and Websites. Compounding the predicament

of accurate mouse phenotyping is the shortage of veterinary

pathologists (mouse pathologists) and physician pathologists

with whom scientific researchers may collaborate. This special

issue on genetically engineered mice touches on some of the

issues facing pathologists as we work with these mice. The goal

of this issue is in part to highlight and discuss some of the com-

plexities of evaluating the histopathological findings as a result

of gene modification in mice. The issue starts with the history

of genetically engineered mice and strategies for designing

phenotyping studies. Following this are articles with specific

considerations for the evaluation of genetically engineered

mice from the embryo to the aged, including methods, new

mouse models of disease, and valuable reference publications

for the veterinary pathologist. We hope that this issue, which

includes many color images as well as a supplement of selected

on-line scanned slides (http://vet.sagepub.com and click on

SAGEscope), will serve as a resource for pathologists and other

researchers alike in their search to better understand gene

function and disease.

R. S. Sellers

Associate Editor, Animal Models of Disease

J. M. Ward

Associate Editor, Laboratory Animals

Veterinary Pathology49(1) 4ª The Author(s) 2012Reprints and permission:sagepub.com/journalsPermissions.navDOI: 10.1177/0300985811429810http://vet.sagepub.com

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