Changes

[[Image:Lab_rat.jpg|200px|thumb|right|'''Lab Rat''' Source: WikiMedia Commons Author: Jean-Etienne Poirrier (2007)]]

|linkpage =Laboratory Animal Pathology - Pathology

|linktext =Laboratory Animal Pathology

|maplink = Laboratory Animal Pathology (Content Map) - Pathology

==Introduction==

==Introduction==

<ref>Krinke, George J. (2000). "History, Strains and Models". ''The Laboratory Rat (Handbook of Experimental Animals)''. Bullock, G.R., Bunton, T. (Eds.). Academic Press. pp. 3–16.</ref> Laboratory rats belong to the species ''Rattus norvegicus'' and are bred and kept for scientific research.  They are and have been used in experimental studies that have added to our understanding of genetics, disease, pharmacology, psychology and other fields.

<ref>Krinke, George J. (2000). "History, Strains and Models". ''The Laboratory Rat (Handbook of Experimental Animals)''. Bullock, G.R., Bunton, T. (Eds.). Academic Press. pp. 3–16.</ref> Laboratory rats belong to the species ''Rattus norvegicus'' and are bred and kept for scientific research.  They are and have been used in experimental studies that have added to our understanding of genetics, disease, pharmacology, psychology and other fields.

They originate from wild brown rats.  The process of domestication started in Europe during the 18^th century, during which wild rats were caught for food and rat-baiting.  Occasionally, albino rats were trapped and these were kept as pets or show animals.  The first time one of these albino mutants was brought into a laboratory for a study was in 1828, in an experiment on fasting.

They originate from wild brown rats.  The process of domestication started in Europe during the 18^th century, when wild rats were caught for food and rat-baiting.  Occasionally, albino rats were trapped and these were kept as pets or show animals.  The first time one of these albino mutants was brought into a laboratory for a study was in 1828, in an experiment on fasting.

Domestic rats differ from wild rats in that they are calmer, less likely to bite, can tolerate greater crowding, breed earlier and are more prolific.  Also, their brains, livers, kidneys, adrenal glands and hearts are smaller.

Domestic rats differ from wild rats in that they are calmer, less likely to bite, can tolerate greater crowding, breed earlier and are more prolific.  Also, their brains, livers, kidneys, adrenal glands and hearts are smaller.

===Strains, Stocks and Transgenics===

===Strains, Stocks and Transgenics===

All rat populations used in research can be included in one of these three groups. Figure 1 is based on a PubMed search of the number of papers using the designated strain or stock for the years 2001-2005 [http://www.isogenic.info/html/rat_strains.html-http://www.isogenic.info/html/rat_strains.html].

[[Image:Rat usage picture.jpg|thumb|right|200px|'''Figure 1:''' ''Usage of different rat types in research articles from 2001 to 2005'' <br> Krinke, George J. (2000)]]

The vast majority of work (76%) was done using outbred Sprague-Dawley or Wistar rats.  Inbred strains were used on only 12% of occasions.  Of the inbred strains, the most widely used was F344 (32.1%), followed by LEW (22.5%). Mutants (=transgenic) were used only in 1% of the studies, reflecting the circumstances explained below.

====Stocks (~outbred strains)====

====Stocks (~outbred strains)====

A '''stock''' is an outbred population (frequently these are termed '''outbred strains''').  These are used when identical genotypes are unnecessary or a random population is required.  Examples:

A '''stock''' is an outbred population (frequently these are termed '''outbred strains''').  These are used when identical genotypes are unnecessary or a random population is required.  Examples:

:* '''''Wistar:'''''  First rat stock developed as a laboratory model and still one of the most popular.  More than half of all laboratory rat strains are descended from this stock (''e.g.'' Sprague Dawley, Long-Evans).  They have wide head, long ears and a tail shorter than the body.

:* '''''Wistar:'''''  First rat stock developed as a laboratory model and still one of the most popular.  More than half of all laboratory rat strains are descended from this stock (''e.g.'' Sprague Dawley, Long-Evans).  They have wide head, long ears and a tail shorter than the body.

:* '''''Sprague Dawley:''''' Multipurpose breed of albino rat used extensively in medical research due to its calmness, ease of handling.  They are prolific (average litter: 10.5), with a lifespan of 2.5-3.5 years and a tail longer than the body.

:* '''''Sprague Dawley:''''' Multipurpose breed of albino rat used extensively in medical research due to its calmness and ease of handling.  They are prolific (average litter: 10.5), with a lifespan of 2.5-3.5 years and a tail longer than the body.

:* '''''Long-Evans:'''''  Multipurpose model organism (frequent in behavioral and obesity research).  Developed by crossing Wistar females with a wild gray male.  They are white with a black or brown hood.

:* '''''Long-Evans:'''''  Multipurpose model organism (frequent in behavioral and obesity research).  Developed by crossing Wistar females with a wild gray male.  They are white with a black or brown hood (=head and shoulders).

 

[[Image:Inbred_rat_lines.jpg|thumb|200px|'''Zucker Rat''' <br> Joanna Servaes 2006, WikiMedia Commons]]

[[Image:Inbred_rat_lines.jpg|thumb|300px|Inbred rat lines. © Charles River Laboratories]]

====Strains (~inbred strains)====

====Strains (~inbred strains)====

====Transgenic rats====

====Transgenic rats====

Most of the techniques used for genetic manipulation depend upon the culture and manipulation of embryonic stem cells (eES).  eES techniques are relatively difficult in rats compared to mice and for this reason, transgenic rats are not commonly used in scientific research.  However, in 2003 researchers succeeded in cloning two laboratory rats by nuclear transfer <ref>Zhou Q ''et al.'' (2003) "Generation of fertile cloned rats by regulating oocyte activation". ''Science'', 302, pp. 1179</ref>. and the rat genome is now available <ref>Rat Genome Sequencing Project Consortium (2004) "Genome sequence of the Brown Norway rat yields insights into mammalian evolution". ''Nature''. 428, pp. 493-521</ref>.  For these reasons, usage of transgenic rats may increase in the near future.  These are the most common types of genetic modification:

Most of the techniques used for genetic manipulation depend upon the culture and manipulation of embryonic stem cells (eES).  eES techniques are relatively difficult in rats compared to mice and for this reason, transgenic rats are not commonly used in scientific research.  However, in 2003 researchers succeeded in cloning two laboratory rats by nuclear transfer <ref>Zhou Q ''et al.'' (2003) "Generation of fertile cloned rats by regulating oocyte activation". ''Science'', 302, pp. 1179</ref>. and the rat genome is now available <ref>Rat Genome Sequencing Project Consortium (2004) "Genome sequence of the Brown Norway rat yields insights into mammalian evolution". ''Nature''. 428, pp. 493-521</ref>.  For these reasons, usage of transgenic rats may increase in the near future, as rats are more appropriate models than mice in specific situations.  These are the most common types of genetic modification:

:* '''''Knock-out '''''animals have a single gene turned off through a targeted mutation (gene trapping).  They are mostly used as human disease models, for the study of gene function and for drug discovery and development.  The technology for production of knock out rats has evolved significantly during the last years and rat models for the study Parkinson\’s, Alzheimer\’s, hypertension, and diabetes are now available commercially [http://www.knockoutrat.org/].

:* '''''Knock-out '''''animals have a single gene turned off through a targeted mutation (gene trapping).  They are mostly used as human disease models, for the study of gene function and for drug discovery and development.  The technology for production of knock out rats has evolved significantly during the last years and rat models for the study Parkinson\’s, Alzheimer\’s, hypertension, and diabetes are now available commercially.

:* '''''Knock-in '''''animals have a single gene insertion in a specific locus (it is targeted too).  This is currently done in mice.

:* '''''Knock-in '''''animals have a single gene insertion in a specific locus (it is targeted too).  This is currently done in mice.

:* '''''Conditional Knock-out/in '''''animals have modified genes that can be knocked-out or knocked-in by manipulation of the environment or administration of a drug.  This provides researchers with added flexibility in experimental design.  Also in this case these manipulations are mostly conducted in mice.

:* '''''Conditional Knock-out/in '''''animals have modified genes that can be knocked-out or knocked-in by manipulation of the environment or administration of a drug.  This provides researchers with added flexibility in experimental design.  Also in this case these manipulations are mostly conducted in mice.

==Anatomy and Histology==

==Anatomy and Histology==

[[Image:Ventral organ layout rat.jpg|thumb|left|400px|Organ topography in the rat, ventral view.]]

[[Image:Ventral organ layout rat.jpg|thumb|left|200px|Organ topography in the rat, ventral view.]]

 

This summary <ref name="Percy"> Percy, D.H. and Barthold, S.W. (2007). “Rat”, In: ''Pathology of laboratory rodents and rabbits''. Percy, D.H. and Barthold, S.W. (Eds.). Blackwell Publishing. pp. 125-178</ref><ref name="Boorman">''Pathology of the Fischer Rat'' (1990). Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery Jr., C.A., MacKenzie, W.F., (Eds.). Academic Press Inc.</ref> is not comprehensive and it only aims to deal with peculiarities of rat anatomy and histology.  The information on gross anatomy is from a reference on F344 rat and minor variations with other strains should be expected:

 

This summary <ref> Percy, D.H. and Barthold, S.W. (2007). “Rat”, In: ''Pathology of laboratory rodents and rabbits''. Percy, D.H. and Barthold, S.W. (Eds.). Blackwell Publishing. pp. 125-178</ref><ref>''Pathology of the Fischer Rat'' (1990). Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery Jr., C.A., MacKenzie, W.F., (Eds.). Academic Press Inc.</ref> is not comprehensive and it only aims to deal with peculiarities of rat anatomy and histology.  The information on gross anatomy is from a reference on F344 rat and minor variations with other strains should be expected:

===Nervous system===

===Nervous system===

The '''''brain''''' is lissencephalic.

The '''''brain''''' is lissencephalic. The '''''spinal cord''''' is 11-12.5cm long and ends in the second lumbar vertebra.

 

The '''''spinal cord''''' is 11-12.5cm long and ends in the second lumbar vertebra.

===Vascular system and blood===

===Vascular system and blood===

The '''''heart''''' of a young adult rat is approximately 0.3% of the body weight.

The '''''heart''''' of a young adult rat is approximately 0.3% of the body weight. In the '''''blood''''' The predominant leukocyte is the lymphocyte (80%).  Eosinophils tend to have ring-shaped nuclei without lobation.  Mature male rats have higher leukocyte counts than females

 

In the '''''blood''''' The predominant leukocyte is the lymphocyte (80%).  Eosinophils tend to have ring-shaped nuclei without lobation.  Mature male rats have higher leukocyte counts than females

===Respiratory system===

===Respiratory system===

The '''''trachea''''' is slightly flattened (3mm x 2mm diameter).

The '''''trachea''''' is slightly flattened (3mm x 2mm diameter).

 

The '''''lung''''' has a single left lobe and four right lobes that follow the bifurcations of the bronchial tree (anterior (=apical or cranial), middle (=cardiac), median (=azygous or accessory) and posterior (=caudal)).  When the bronchi enter the lung, they divide into a major segment (at a small angle from the parent airway) and a minor segment (at a much greater angle to the parent airway).  This results in air moving at lower velocity entering the minor branch.  This is called ''monopodal branching'' and is a feature of the rat and the mouse.  A feature particular of rats is the presence of serous cells in the respiratory epithelium.

The '''''lung''''' has a single left lobe and four right lobes that follow the bifurcations of the bronchial tree (anterior (=apical or cranial), middle (=cardiac), median (=azygous or accessory) and posterior (=caudal)).  When the bronchus enter the lung, they divide into a major segment (at a small angle from the parent airway) and a minor segment (at a much greater angle to the parent airway).  This results in air moving at lower velocity entering the minor branch.  This is called ''monopodal branching'' and is a feature of the rat and the mouse.  A feature particular of rats is the presence of serous cells in the respiratory epithelium.

 

 

===Lymphoid system===

===Lymphoid system===

===Digestive system===

===Digestive system===

[[Image:Ventral_neck_organs_rat.jpg|thumb|400px|Ventral neck organs in the rat.]]

[[Image:Ventral_neck_organs_rat.jpg|thumb|200px|'''Rat Incisors''' <br> Alexey Krasavin 2007, WikiMedia Commons]]

'''''Oral cavity:''''' The dental formula of the rat is 2(I 1/1; M 3/3).  Incisors are continuously erupting and are maintained at a constant length by attrition of occlusal surfaces.  This results in total renewal every 40-50 days.  Their yellow colour increases with age and is a result of iron containing pigments.

'''''Oral cavity:''''' The dental formula of the rat is 2(I 1/1; M 3/3).  Incisors are continuously erupting and are maintained at a constant length by attrition of occlusal surfaces.  This results in total renewal every 40-50 days.  Their yellow colour increases with age and is a result of iron containing pigments.

   

   

The major '''''salivary glands''''' are located along the ventral neck and extend upward to the base of the ear in close association with the mandibular lymph nodes and extraorbital lacrimal gland.  There is sexual dimorphism in salivary glands: Male parotids and submandibular glands are twice the size than females’, with increased secretory granules in the cytoplasm of serous cells.

The major '''''salivary glands''''' are located along the ventral neck and extend upward to the base of the ear in close association with the mandibular lymph nodes and extraorbital lacrimal gland.  There is sexual dimorphism in salivary glands: Male parotids and submandibular glands are twice the size of females’, with increased secretory granules in the cytoplasm of serous cells.

'''''Oesophagus:'' ''' The soft palate is long.  As a result of this, the oesophageal opening, epiglottis and larynx are cranial to the nasopharyngeal opening.

'''''Oesophagus:'' ''' The soft palate is long.  As a result of this, the oesophageal opening, epiglottis and larynx are cranial to the nasopharyngeal opening.

'''''Liver:'' ''' The liver has four lobes (left, median, right and caudate).  The median, right and caudate lobes are subdivided in two sublobes.  The rat has no gall bladder and the bile is not concentrated.  Hepatocyte polyploidy and binucleated cells is common and increases with age  

'''''Liver:'' ''' The liver has four lobes (left, median, right and caudate).  The median, right and caudate lobes are subdivided in two sublobes.  The rat has no gall bladder and the bile is not concentrated.  Hepatocyte polyploidy and binucleated cells is common and increases with age  

===Urogenital system===

===Urogenital system===

==='''Integument'''===

==='''Integument'''===

The rat has two types of '''''hair follicles''''': (a) ''larger follicles'' containing longer, thicker hairs and (b) ''smaller follicles'' with shorter finer hairs.  Several smaller follicles are arranged around a central large follicle.  All follicles can contain one or more hair shafts.  The epidermis at the opening of hair follicles is thickened (4-6 cells), these areas are known as Haarscheibe plaques.  ''Tactile hairs'' are found around the muzzle and have follicles with prominent vascular sinusoids, nerve endings and abundant interspersed striated muscle fibres.   

The rat has two types of '''''hair follicle''''': (a) ''larger follicles'' containing longer, thicker hairs and (b) ''smaller follicles'' with shorter finer hairs.  Several smaller follicles are arranged around a central large follicle.  All follicles can contain one or more hair shafts.  The epidermis at the opening of hair follicles is thickened (4-6 cells); these areas are known as Haarscheibe plaques.  ''Tactile hairs'' are found around the muzzle and have follicles with prominent vascular sinusoids, nerve endings and abundant interspersed striated muscle fibres.   

There are '''''eccrine glands''''' in the dermis of the digital pads.

There are '''''eccrine glands''''' in the dermis of the digital pads.

===Other===

===Other===

As mice, rats have prominent '''''brown fat''''', as a subcutaneous pad over the shoulders, neck, axillae and peritoneal tissue.  The '''''fur''''' of male albino rats tends to yellow with age.

As in mice, rats have prominent '''''brown fat''''', as a subcutaneous pad over the shoulders, neck, axillae and peritoneal tissue.  The '''''fur''''' of male albino rats tends to yellow with age.

==Diseases==

==Diseases==

===Congenital and genetic===

===Congenital and genetic===

===Nutritional and Environmental===

===Nutritional and Environmental===

===Degenerative and Aging===

===Degenerative and Aging===

===Infectious===

===Infectious===

====Bacterial====

====Bacterial====

====Viral====

====Viral====

====Parasitic====

====Parasitic====

====Mycotic====

====Mycotic====

===Neoplasia===

===Neoplasia===

====Pulmonary lesions of unknown aetiology====

====Pulmonary lesions of unknown aetiology====

==The rat in toxicopathology==

==The rat in toxicopathology==

==References==

==References==

<references/>

<references/>