The letter N used in a strain designation denotes the nuclear or backcross generation, followed by the number.  Mouse genes are always written in italics with the first letter capitalized (Lepr); the protein produced as a result is in all caps with no italics (LEPR). Human genes are written in all caps italics (APOA1), and the proteins in all caps (APOA1). Alleles are written in italics superscripted to the gene symbol (Apc^Min). Note that if the mutation is dominantly inherited it begins with a capital letter, and if it's recessive it's not capitalized (i.e. db is recessive). When both the mutant allele and the gene are known, both are used (Lepr^db).

Spontaneous, chemical, or radiation-induced mutant names begin with the genetic background strain, followed by a hypen. At first, the mutation is given a descriptive symbol such as lpr for lymphoproliferation. Once the gene has been identified, its function-based symbol is then used, i.e. Fas^lpr.

Coisogenic, congenic, and segregating inbred strains are even more complex. The background or host strain is listed first, followed by a period or hyphen, then the symbol of the donor strain, a hyphen, and the locus and allele in italics. For example, the coisogenic strain AKR/J-nu^str is an AKR with the mutation nustr in the nude locus; by definition all coisogenic strains arise as a result of mutation within an inbred strain. A heterozygote would be indicated AKR/J-+/nustr. The congenic strain C57BL/6J.PL/J-Thy-1^a is a C57BL/6J background mouse with the a allele in the Thy-1 locus transferred to it from a PL/J mouse{3564}. If there are several available lines from the same donor strain, they may be distinguished by a number and/or letter in parentheses, i.e. B10.129(10M)-H11^b/Sn. Incipient congenic strains have been backcrossed onto the inbred strain for 5-9 generations (indicated by N5-N9); after that they are congenic (N10+).

Sometimes the donor strain of a congenic strain was a mixture, i.e. of the strain donating the ES cells (usually 129) and the recipient strain. In this case the donor and recipient strains are separated by a semicolon.

Targeted mutations (knockouts or knockins): C57BL/6 x B6;129P2-Apoa1^tm1Unc indicates a cross between C57BL/6 and a mixed B6 strain receiving ES cells from the 129 line carrying the targeted mutation and backcrossed for <5 generations. The congenic strain would be B6.129P2-Apoa1^tm1Uncafter at least 5 generations of backcrossing (N5).

There are two types of congenic strains:

Consomic strains: repeated backcrossing of a whole chromosome such as the X or Y onto an inbred strain. The appended chromosome is listed with its strain of origin after the host strain symbol, i.e. C57BL/6J-Y^AKR{4184}.

Conplastic strains: backcrossing the mitochondrial genome of one strain onto the nuclear genome of another, i.e. C57BL/6J-mt BALB/c{4184}.

Recombinant inbred strains are denoted by the abbreviations of the progenitor strains separated by an X. Individual member of a set of RI strains are identified by a unique number or letter suffix after a hyphen, i.e. AKXD-1 is one strain of a cross of AKR and DBA/2J.{4184}

Transgenics have extra information added to the rules for congenics. The general format is

TgX(YYYYYY)#####Zzz

The Tg symbol is followed by a letter indicating the mode of production (N=nonhomologous or DNA injection, R=retroviral, H=homologous or ES cell). In parentheses, information about the inserted gene is given, in no more than 6-8 characters and without italics, superscripts, subscripts, internal spaces or punctuation. First, the number of the chromosome into which the gene was inserted is indicated, or a zero if unknown. Next, a description of the species of origin and the gene (MMU=Mus musculus, RNO=Rattus norvegicus, HSA=Homo sapiens) follows. After the close parenthesis, the laboratory assigned number (######) and laboratory registration code (Zzz) are listed.{4184} Examples are: {3564}{3929}

1. C57BL/6J-Tg(0HSAHba)As12 is a transgenic C57Bl/6J mouse with the gene for human (HSA) hemoglobin alpha-chain (Hba) inserted in an unknown location (0), created by the 12^th insertion performed at the University of Arhus.{3564}

2. C57BL/6J-TgN(CD8Ge)23Jwg is the human CD8 genomic clone (Ge) inserted into a C57BL/6 mouse from Jax; the 23^rd mouse screened in a series of microinjections in the laboratory of Jon W. Gordon.{3929}

3. Crl:ICR-TgN(SVDhfr)432Jwg is the SV40 early promoter driving a mouse dihydrofolate reductase (Dhfr) gene; 4 kilobase plasmid; the 32^nd animal screened in the laboratory of Jon W. Gordon. The ICR outbred mice were from Charles River.{3929}

Nomenclature of rat stocks and strains

Common outbred strains are the Sprague-Dawley, Long-Evans (a hooded rat), Wistar, and Holtzman. Inbred strains are ACI, BN (Brown-Norway), BUF (Buffalo), F344, LEW (Lewis), SHR (spontaneously hypertensive) and WF (Wistar-Furth). Mutant strains include Brattleboro (autosomal recessive diabetes insipidus), Gunn (autosomal recessive jaundice), Nude (autosomal recessive T cell deficient) and Obese SHR (autosomal recessive type 4 hyperlipoproteinemia).{2764} 

The BB rat (BioBreeding) develops acute insulin-dependent diabetes mellitus similar to human type I IDDM. The gene may be associated with a "T lymphopenia" gene. Rats develop insulitis, hyperglycemia, no measurable insulin, ketoacidosis, and PU/PD between 6 weeks and 6 months. Insulin must be administered daily. The etiology appears to be autoimmune. All T cell types are severely decreased due to a post-thymic defect; B cells are normal and neutrophils are increased because of chronic respiratory infection. They should be housed in laminar-flow, SPF or gnotobiotic conditions. Breeding success is improved by giving cyclosporin A, which delays onset of diabetes.{4162}

BB rats were crossed with obese Zucker rats carrying the fa gene to produce the BBZ/Wor diabetic rat. They are similar to BB/Wor rats in T cell defects, but do not require insulin possibly because of incomplete pancreatic beta cell destruction.{4162}

Nomenclature is standardized under the auspices of the International Committee on Laboratory Animals (ICLA). Outbred stocks are denoted somewhat differently from inbreds, since less is known about them. For outbreds, the supplier or breeder code is indicated first with a capital letter and one or more lower case letters, followed by a colon. Next are capital letters designating the stock, followed by letters in parentheses denoting the stock origin. Finally, subscript symbols are used to indicate the method by which the rats were reared if not by their natural mother (i.e. f=fostered, fh=fostered by hand).{2764}

Nomenclature for inbred rats was published in 1973 and 1992. For inbreds, the strain is given in capital letters followed by a slash. Substrain is given as either numbers (indicating the substrain was derived from a common strain but separated before the completion of inbreeding) or as individual or company codes. The same subscripts are used for rearing method.{2764} The NAS publishes a directory of sources of laboratory animals in the US and Canada, listing rodents according to standard nomenclature ("Animals for Research", 1979).

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Anatomy{3986}

	Vertebral formula: C7 T13 L6 S4 C27-30; ossification complete at 1 year
	Dental formula: I 1/1 C0/0 PM 0/0 M3/3 = 16; incisors hypsodont, molars brachiodont incisors erupt around day 10; occlusion occurs by day 16 (Lab Animal 30(4):21, 2001)
	Chromosomes numbered with Arabic numerals in decreasing order of size; mouse has 20 pairs{3551} (numbered 1-19 plus X/Y); rat has 21 pairs numbered RNO1 etc.{4189}
	Brain surface is smooth; the rat lacks a foramen of Magendie
	Rats and mice have 2 anterior venae cavae. In the rat the right vena cava joins the right atrium and the left joins the azygous vein before joining the caudal vena cava. In the mouse, both venae cavae join the right atrium.
	Lungs: one left lobe, 4 right lobes (cranial, middle, caudal, postcaval); the tracheal rings have a C-configuration until the level of the bronchi where they are circular
	Brown fat between the scapulae, axillary, cervical, jugular veins, thoracic aorta, kidney hilus, urethra; used for thermogenesis (via norepinephrine action, CTLAS 39(3):23, 2000)
	Liver has 4 lobes; in the mouse the median lobe surrounds the gall bladder; the rat lacks a gall bladder
	Stomach has a limiting ridge that prevents vomiting
	Rats have greatly reduced nictitating glands, which in part accounts for why their eyes appear to bulge prominently. Tears are produced by the Harderian gland medially and the lacrimal glands (a small intraorbital and a larger exorbital) laterally.{3583}
	Rats have five digits on forelimbs and hindlimbs, with the thumb much reduced in size and having a flattened nail. Walking pads or tori number five apically, three interdigitally and two basally on the forelimb.{3583} (Note: Army board question quotes Hillyer & Quesenberry that all except gerbils have 4 front and 5 hind)
	Although the rat skeletal system is much like that of other mammals, there are a few minor differences. Both rib segments are usually ossified, and the rat does not have true costal cartilage. The clavicle is connected to the sternum via the osmosternum, proximal and distal procoracoid pieces. Only the clavicle and sternum are ossified; the others are cartilaginous structures.{3583} Rats do not have Haversian systems in their long bones.
	Head and neck structures have been clearly defined in the rat. There are two lacrimal glands, the larger exorbital gland located ventro-rostral to the ear, and the intraorbital gland located in the caudal angle of the orbit. The duct of the exorbital gland joins that of the intraorbital and opens onto the conjunctiva on the dorsolateral aspect of the eye. Lacrimal duct epithelium of the rat secretes chloride, potassium and sodium. The Harderian gland, thought to be present in most mammals, is horseshoe-shaped and occupies a large portion of the orbit, even encircling the optic nerve. Secretory cells have fat globules, particularly in swimming animals. The Harderian gland has both apocrine and holocrine functions.{3583}
	Steno’s gland is the largest of the numerous rostral nasal glands, and has features similar to those of a serous salivary gland. However, its duct empties into the vestibule, and so it is homologous with the salt gland of marine birds. Its secretions act to humidify inspired air and contribute to the mucous blanket of the ciliated respiratory epithelium.{3583}
	There are three pairs of salivary glands in the rat: the parotid, submandibular or submaxillary, and the sublingual.{3583}
	Pancreatic exocrine system: Humans have a major duodenal papilla near their bile duct, and an accessory duct entering at the minor papilla. The rat has 15-40 pancreatic ducts, all of which empty into the bile duct. If cannulated near the liver, only bile will be collected. If cannulated further distally, a mix of bile and pancreatic secretions is collected.{4003}
	Male reproductive anatomy: vesicular glands (seminal vesicles), coagulating glands, prostate with 2 pairs of lobes (dorsal and ventral), paired bulbourethral glands. The rat's penis is directed ventrocaudally and has a small os penis. Rat scrotal size is directly related to age.{3583}
	Female reproductive anatomy: rat has 2 cervices and a duplex uterus (mouse has only one) ; rat has 6 pairs of mammary glands (3 pectoral and 3 abdominal), mouse has 5 pairs
	Rodents have hemochorial placentation (Army board, Percy & Barthold p9-10)
	Rat vagina located 7 mm ventral to anus, and there is a small prepuce containing the clitoris 4 mm cranial to the vagina{3583}
	The adrenal medulla of young female mice <70 days old contains a zone of reddish cells termed the "X-zone". This can confuse some toxicologic studies. (Note: an Army board question quoted Percy & Barthold as saying it disappears "when males reach sexual maturity and females undergo their first pregnancy")
	Male and female mice can be distinguished by looking at the Bowman’s capsule around the glomerulus. In males the cells are cuboidal, whereas in females and juvenile mice the cells are flattened.

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Physiology{3986}

Normal values          Nutrition       Reproduction          

Normal physiologic values:

	Rat	Mouse	Guinea pig
Temperature, °F	97-102	95-102.5	102-103
Heart rate, beats/min	330-480	320-780	230-380
Respiratory rate, /min	66-114	84-280	42-104
Urine volume	3.3ml/100gm/day	0.5-1 ml/day total

For a table of thermoneutral zones, click here.

The major glucocorticoid in rats is corticosterone. Plasma levels will peak within 2 hours of a stressor. The normal levels fluctuate with circadian rhythm, peaking just prior to and during the beginning of the dark cycle at 145-234 ng/ml.{3731}

Procaine, used in some antibiotic preparations such as penicillin-streptomycin, is toxic to rabbits, guinea pigs and mice.{4177}

Nutrition

Rats eat 5-6gm/100gm body weight/day; mice eat 12-18gm/100gm/day (more than most any lab animal) {4742}and are more sensitive to vitamin and mineral imbalances{3986}. Mice consume 3-5 gm feed per day from weaning throughout life. Outbreds gain weight faster and mature heavier than inbreds.{3551}

 

Nutrient	Mouse{3551}	Rat{3580}
Crude protein	20-25%	12%
Fat	5-12%	5-15%
Fiber	2.5%
Carbohydrate	45-60%	3800kcal/kg DE

 

Water: rats drink 1ml/10gm/day; mice drink 1.5ml/10gm/day{3986}.

Mice are more sensitive than most animals to water loss, because of their size (surface area per gram of body weight is very high). Adult mice need to drink 6-7ml of water per day. Water conservation is closely linked to thermoregulation; if it gets too hot a mouse would die of dehydration. Mice have no sweat glands and cannot pant, and they don’t salivate much either. Therefore they compensate for hot temperatures by raising their body temperatures as much as 4° C (i.e. from 33.8° to 37.2°), decreasing metabolic rate, and losing heat through their ears. The mouse’s thermoneutral zone is narrower than for any other mammal, in the range 29.6°-30.5°C; but for optimal growth the room should be kept at 21° -25°C.{3551}

A huge body of dietary research results from work with the laboratory rat. In experimental studies of tumorigenesis, toxicity, hepatic microsomal enzymes, neurotransmitters and other areas the diet has been shown to exert extensive effects upon the results.{3580}

Adult rats can manage on a diet containing 2.5-5kcal DE/gm of feed (110kcal DE/kg body weight^.75), but weanlings require at least 3kcal/gm, pregnant females need 10-30% more, and lactating rats need 2-4 times the energy of nonlactating females. Most purified or chemically defined diets contain 4-4½ kcal GE/gm of which 90-95% is digestible and of that 90-95% is metabolizable. Rats apparently eat to satisfy their caloric needs, and then their protein needs, in general.{3580}

Fatty acids are necessary for synthesis of tissue lipids including those in the skin, absorption of fat-soluble vitamins, and prostaglandin formation. Fat-deficient rats grow more slowly, have scaly thin skin, rough thin haircoats, tail necrosis, fatty liver, renal damage and ECG abnormalities. Since most foods contain linoleic acid (which the rat can use to produce arachidonic acid), induction of FA deficiency requires use of vitamin-free casein as a protein source and sucrose for carbohydrate.{3580}

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Reproduction

	Rat	Mouse
Puberty, days	40-60	28-49 female, 49-56 male
First fertile mating, weeks	9	7-10
Gestation, days	19-23	18-21

 

Stages of the estrous cycle seen with cytology:{4139}

1. Proestrus: >50% intermediate epithelial cells, fewer parabasals , very few PMNs

2. Estrus: Squamous epithelial cells, nuclei absent or pyknotic

3. Metestrus: Mostly PMNs and squamous epithelial cells, few parabasals

4. Diestrus: mostly PMNs and some parabasals, no older epithelial cells

 

Criteria used to determine stages of estrus on mouse vaginal smears{4139}

	Epithelial cells			PMNs
	Parabasal	Intermediate	Cornified
Proestrus	>25%	0-25%	0-25%	<10%
Estrus	<25%	0-25%	>50%	0
Metestrus	>=25%	>=25%	>=25%	>=25%
Diestrus	0-25%	0-25%	0-25%	>50%

	Estrous cycle is 4-5 days, polyestrous. Estrus occurs at night after day 3 of the cycle, lasting for 12-14 hours. Ovulation is within 8-12 hours after the onset of estrus in mice, but during metestrus in rats (personal communication, Lisa Halliday, 4/14/00 CL Davis seminar). Rats can be induced to ovulate with forced breeding{3764}.
	Breeding dates are established in rats by either the presence of sperm in vaginal smears, or the presence of a copulatory plug. Abdominal enlargement is evident at about 14 days; pseudopregnancy is rare.{2764}
	Rats are very sensitive to light levels. Persistent estrus, hyperestrogenism, polycystic ovaries and endometrial hypertrophy can occur after 3 days of continuous lighting{2764}.
	Whitten effect: synchronization of estrus induced by introduction of male{3987}; occurs to a lesser extent in rats{2764}
	Bruce effect: termination of pregnancies (abortion or prevention of implantation) at 4 days when a strange male introduced.{3987, 3551}
	Lee-Boot effect: irregular or suppressed estrus in the absence of male{3987}; female mice housed together isolated from males tend to cease cycling and remain in anestrus or pseudopregnant state{4139}
	Vandenburgh effect: presence of adult males accelerates puberty in females

In some experiments, such as induction of infection with Neisseria gonorrheae, female mice must be in estrus in order for infection to be successful. In other situations, such as synchronization of estrus for timed mating, it is also advantageous to have an entire group of females in the same stage of their cycles. Exogenous hormone is often used to force estrus (i.e. estradiol, or PMSG followed by HCG). Alternatively, a period of 21 days or so of housing females away from the pheromonal stimulation of males (i.e. in Horsfall units or ventilated racks) will enhance the induction of estrus by means of adding male urine-soaked bedding to the females' cages. In other words, utilization of the Lee-Boot effect by housing separately for 21 days can greatly enhance the Whitten effect. When housed for 21 days prior to male urine exposure, 88% of females were in either proestrus or estrus after a 4-day urine exposure. When a 7-day acclimation period was used, only 76% were in estrus or proestrus after 4 days of urine exposure.{4139}

	Vaginal smears can be stained with methylene blue or with blood stains.
	Place males alone in cage for a day or so before adding females; mating occurs during the dark phase; vaginal plug composed of secretions from male vesicular and coagulating glands.{3551,3929}
	Rats and mice both have vaginal plugs; in mice these persist for 16-48 hours.
	Females can be mated during post-partum estrus 14-28 hours after parturition if male is left in cage; gestation will be prolonged to 21-25 days.{3551, 3929, 3986}
	Gestation length varies with strain or stock.
	Litter size 1-12 pups (mice){3551}, 6-12 pups (rats).{2764}
	Lactation lasts for 21 days. In rats, the gut remains open to colostral antibodies for up to 18 days{2764}. Pups are weaned when they weigh 9-10 gm (mice) or at 21 days of age.

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Multimammate Rats

Because some taxonomists believe the genus Mastomys is a subgenus of Praomys, the correct way to indicate genus and species of the most common of the multimammate rats is Praomys (Mastomys) natalensis. They are among the most abundant rodents in Africa.{3560} However, they are named in the Lacey Act and their import into the US may be restricted. A newer reference calls them "African multimammate mice" and uses Mastomys coucha as the proper name.{2375}

This murine rodent also lacks a gall bladder. The number of mammary glands, 8-12 pairs but sometimes as many at 18, is unusually large. The female has a well-developed prostate gland. In captivity they breed well, with a short interval between litters and early onset of puberty. When disturbed, however, mothers may cannibalize their litters. They are nervous animals, are difficult to handle, and may bite seemingly without provocation.{3560}

Multimammate rats are useful in research because they are unusually susceptible to Yersinia pestis. They are used both for routine diagnostics and for development of vaccines. They have also been used as experimental hosts for Brugia, Litomosoides carinii (carried by the mite Ornithonyssus bacoti), Toxoplasma and Schistosoma. In addition, the multimammate rat is the only known nonhuman host of Lassa virus. In captivity they frequently develop adenocarcinoma of the glandular stomach. The well-developed prostate in females has been studied for the effects of hormones.{3560} Neonates infected with parvovirus (either H-1 or MVMp) show signs of hair color changes (white or gray), growth disturbances, and in the case of MVMp, death at weaning age (>60%). Targets of the virus are likely intestine, liver, and hematopoietic cells. Because of the pathogenicity of mouse and rat parvoviruses for multimammate mice, they are not likely to be good candidates for parvoviral-vectored genes.{2375}

Most multimammate rats that survive to over 2 years of age suffer from spontaneous osteoarthritis, particularly in the vertebrae and diarthrodial joints. The elbows and stifles are most severely affected. In males, there is often intervertebral disc degeneration. Affected animals are reluctant to use their hind legs, and may become paraplegic. Another common condition of old age is glomerulonephritis, possibly of immune origin.{3560}

	Adult weight: 40-45 gm
	Life span: 2-3 years, maximum 38 months
	Feed consumption: 6 gm/day
	Chromosome #: 36
	Puberty: 55-75 days
	Estrous cycle: range 6-8 days
	Gestation: 23 days
	Litter size: 8 (5-20)
	Birth weight: 2-3 gm
	Eyes open: 13-7 days
	Weaning: 19-21 days{3560}

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