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Sprague Dawley® Rat Model - Taconic

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<strong>Sprague</strong> <strong>Dawley®</strong> <strong>Rat</strong><br />

The most widely used outbred rat model for research, the<br />

<strong>Sprague</strong> Dawley ® is ideal for applications requiring accurate<br />

estimation of gestational age.<br />

The excellent reproductive performance of the <strong>Sprague</strong> Dawley ® model makes it a<br />

preferred choice for generating timed-pregnant females. <strong>Taconic</strong>’s proven process for<br />

producing this model ensures timed-pregnant rats bearing litters within a 24-hour<br />

window of gestational age.<br />

Options Available:<br />

The preferred choice<br />

for generating timedpregnant<br />

females.<br />

This booklet presents abridged descriptions. For additional information on model origins and pricing as well as<br />

model datasheets and references, please see the <strong>Taconic</strong> website at www.taconic.com.<br />

US: 1-888-822-6642 • custserv@taconic.com | Europe: +45 70 23 04 05 • taconiceurope@taconic.com


<strong>Sprague</strong> Dawley ® <strong>Rat</strong> <strong>Model</strong><br />

The <strong>Sprague</strong> Dawley ® outbred model was developed<br />

by R. Dawley, <strong>Sprague</strong>-Dawley Company, Madison,<br />

Wisconsin, in 1925. NIH received stock in 1945<br />

and <strong>Taconic</strong> later received stock from the NIH<br />

Animal Genetic Resource in 1970. Refreshed with<br />

NIH Genetic Resource stock in 1998, the rats are<br />

maintained by rotational breeding in a closed colony.<br />

Nomenclature: NTac:SD<br />

Characteristics<br />

• Most widely used outbred rat in biomedical<br />

research<br />

• Excellent reproductive performance,<br />

making it an ideal model for generating<br />

timed-pregnant females<br />

• Docile nature<br />

• Coat Color: Albino<br />

• Coat color loci: Tyr c<br />

<strong>Sprague</strong> Dawley ® One Year Growth<br />

6 7 8 9 10 11 12 13 14 15 16 17 18 22 26 30 34 38 42 46 50 54 58<br />

Research Applications<br />

• Toxicology, safety & efficacy testing,<br />

reproduction and development,<br />

behavior, aging, teratology, oncology,<br />

nutrition, and pharmacology studies<br />

• Study of maternal and fetal<br />

infection (Riggs)<br />

• Study of the effects of pre-natal<br />

high-salt diet on offspring<br />

(Porter)<br />

• Study of the effects of sex and<br />

hormonal status on restraint-<br />

stress-induced working memory<br />

impairment (Shansky)<br />

• Study of bone-specific<br />

osteocalcin gene in mouse and<br />

rat (Rahman)<br />

• Study of hippocampal excitability<br />

during the estrous cycle in<br />

rats (Scharfman)<br />

US: 1-888-822-6642 • custserv@taconic.com | Europe: +45 70 23 04 05 • taconiceurope@taconic.com<br />

700<br />

600<br />

500<br />

400<br />

300<br />

200<br />

100<br />

0


<strong>Sprague</strong> Dawley ® Physiological Data<br />

Parameter Units SD Males SD Females<br />

Serum Chemistry Avg±D.D.<br />

Glucose mg/dL 82.4 ± 11.3 93.2 ± 10.3<br />

Creatinine mg/dL 0.3 ± 0.1 0.3 ± 0.1<br />

BUN mg/dL 9.1 ± 1.4 13.6 ± 3.0<br />

Total Bilirubin mg/dL 0.1 ± 0.0 0.1 ± 0.0<br />

Total Protein<br />

Blood Counts<br />

Erythron<br />

g/dL 6.4 ± 0.2 6.7 ± 0.2<br />

Red Blood Cells x106 /µL 6.9 ± 0.3 7.7 ± 0.3<br />

Nucleated RBC x106 /µL 0 0<br />

Hemoglobin g/dL 14.5 ± 0.8 16.1 ± 0.6<br />

Hematocrit % 48.3 ± 2.3 51.2 ± 2.6<br />

MCV fL 69.9 ± 1.7 66.9 ± 0.9<br />

MCH pG 20.9 ± 1.3 21.0 ± 1.1<br />

MCHC<br />

Platelets<br />

% 29.9 ± 1.6 31.4 ± 1.9<br />

Platelets x103 Leukogram<br />

/µL 1358.0 ± 123.8 1262.2 ± 278.4<br />

White Blood Cells x103 /µL 9.4 ± 3.2 6.0 ± 1.5<br />

Neutrophil x103 /µL 0.9 ± 0.5 0.4 ± 0.3<br />

Bands x103 /µL 0 0<br />

Lymphocyte x103 /µL 8.3 ± 2.9 5.5 ± 1.4<br />

Monocytes x103 Urinalysis<br />

/µL 0.3 ± 0.3 0.1 ± 0.1<br />

Glucose mg/dL Negative Negative<br />

Blood Negative Negative<br />

pH 6.75 ± 0.35 6.7 ± 0.4<br />

Protein mg/dL N/A N/A<br />

Specific Gravity 1.0195 ± 0.0068 1.0155 ± 0.0079<br />

Life Span 24 - 36 Months<br />

Food Consumption 4-5g/100g Body Weight<br />

Water Consumption 8-11ml/100g Body Weight<br />

Additional Data n=10<br />

Available at taconic.com/SD<br />

There are three health<br />

standard options available<br />

for <strong>Sprague</strong> Dawley ® :<br />

• Murine Pathogen Free<br />

• Restricted Flora<br />

• Germfree<br />

US: 1-888-822-6642 • custserv@taconic.com | Europe: +45 70 23 04 05 • taconiceurope@taconic.com<br />

<strong>Sprague</strong> Dawley ® <strong>Rat</strong> <strong>Model</strong><br />

Flexible Health<br />

Standard Options<br />

<strong>Taconic</strong> offers the <strong>Sprague</strong> Dawley ® model<br />

at a variety of health profiles, enabling you<br />

to choose a profile that suits the needs of<br />

your specific research project and facility.<br />

Transportation methods for all models are<br />

designed to ensure the integrity and safety of<br />

your animals during shipment.<br />

<strong>Rat</strong>s bred to the Restricted Flora TM (RF)<br />

health standard and Murine Pathogen Free TM<br />

(MPF) health standard are shipped in our<br />

unique <strong>Taconic</strong> Transit CageTM . <strong>Taconic</strong> is<br />

the only commercial supplier of the <strong>Sprague</strong><br />

Dawley ® model at the Germfree (GF) health<br />

standard, delivered in our Germ-Free<br />

Shippers. Regardless of the health standard<br />

selected, <strong>Taconic</strong> <strong>Sprague</strong> Dawley ® rats<br />

provide 95% or greater accuracy on timedpregnant<br />

gestation.


<strong>Sprague</strong> Dawley ® <strong>Rat</strong> <strong>Model</strong><br />

The Role of Timed-Pregnant<br />

<strong>Sprague</strong> Dawley ® <strong>Rat</strong>s in<br />

Biomedical Research<br />

The ability to monitor embryonic development and<br />

accurately determine gestational age of lab animal<br />

embryos is vital in many areas of biomedical research.<br />

For this reason, embryos of timed-pregnant <strong>Sprague</strong>-<br />

Dawley rats are used in the study of embryonic<br />

development, teratology and reproductive toxicology, as<br />

well as experiments using fetal tissue that requires cell<br />

harvesting and culturing at specific embryonic ages.<br />

Critical investigations by R.J. Blandau and his colleagues<br />

more than 50 years ago established procedures<br />

for measuring and timing gestational development<br />

in rats with high accuracy. Monitoring gestational<br />

development requires a reliable determination of the<br />

time of conception. Since no scientific method exists<br />

to determine the exact time of conception, indirect<br />

indicators are used. Vaginal swabs can confirm male<br />

fertility and offer a quantitative indicator of the likelihood<br />

of fertilization, making the presence of sperm in the<br />

vagina of female rats in estrus a reliable indicator<br />

of conception.<br />

The female rat accepts the male for mating only at the<br />

end of the 12-hour preliminary period of proestrus and<br />

during the 12 hours of estrus. Ovulation occurs about<br />

10 hours after the onset of estrus. Sperm migrate<br />

from the uterus to the oviduct about 15 minutes after<br />

copulation; at one hour, sperm are found throughout<br />

the oviduct and at three hours, 90% of the ova are<br />

fertilized. Based on this data, using proper monitoring<br />

and controls, the onset of embryonic development can<br />

be estimated with considerable accuracy.<br />

US: 1-888-822-6642 • custserv@taconic.com | Europe: +45 70 23 04 05 • taconiceurope@taconic.com<br />

Gestational age is measured from the time of<br />

conception, which marks the beginning of embryonic<br />

Day 1. At 24 hours after conception, as Day 2 begins,<br />

the embryo has cleaved or is about to cleave into the<br />

two-cell stage. At the beginning of Day 4, the embryo –<br />

a morula that contains 12 to 16 cells – begins to enter<br />

the uterus. Implantation usually begins on the evening of<br />

Day 5 as the embryo settles into the maternal uterine<br />

wall. Implantation occurs when the blastocyst, or<br />

germinal vesicle, becomes clasped by the endometrium;<br />

the blastocyst orients itself with the inner cell mass<br />

facing the underlying maternal tissue. Estrogen and<br />

other hormonal conditions in the uterus affect the rate<br />

of development at implantation.<br />

During Day 6, the blastocyst increases in size and<br />

elongates. Implantation sites are visually evident by<br />

Day 7. During Days 9 and 10, the beginning of somite<br />

formation takes place. Somites – segments formed on<br />

either side of the embryo’s neural tube – develop into<br />

external body forms as they transform into muscle<br />

mass connected to a spinal nerve. The number of<br />

somites increases at a known progression, which can<br />

be used to track development.<br />

The organogenesis stage begins at Day 5 and continues<br />

for 8 or 9 days. During this period rudimentary<br />

organs, or anlagen, appear. The anlagen undergo<br />

cellular growth, with development branching off or<br />

differentiating toward unique organs and an adult organ<br />

morphology achieved. This is the period of greatest<br />

susceptibility to carcinogens or teratogens, which cause<br />

fetal tumors, malformations or disruption of the normal<br />

development rate.


Following organogenesis, the embryo enters the stage<br />

of maturation, the time when organs grow and become<br />

functionally complete. By Day 15 the embryo’s head<br />

is growing faster than the rump; the previously pearshaped<br />

body evolves into a cylindrical shape; the eyelids<br />

are formed and fused. The bones develop joint cavities<br />

over several days of maturing development. The joint<br />

cavities develop for the shoulder, elbow, hip, and knee<br />

joints during Day 16, the carpal and tarsal joints on Day<br />

17, and the digital joints of the legs during Day 19 or<br />

20. By Day 22, blood-forming activity in the liver nearly<br />

ceases with the end of gestation. Since the gestation<br />

period is 21 to 23 days, Day 22 is the average date<br />

of birth.<br />

Another measure of gestational age is embryo crown-torump-length,<br />

for which standard rates of development<br />

are well documented. The crown-to-rump measurement<br />

is taken from the vertex to the rump, taking care to<br />

45<br />

40<br />

35<br />

30<br />

25<br />

20<br />

15<br />

10<br />

5<br />

0<br />

US: 1-888-822-6642 • custserv@taconic.com | Europe: +45 70 23 04 05 • taconiceurope@taconic.com<br />

<strong>Sprague</strong> Dawley ® <strong>Rat</strong> <strong>Model</strong><br />

Fetal Crown-to-Rump Lengths<br />

avoid caliper pressure that would distort the natural<br />

curvature of the embryo. At Day 11, there are 4 to 13<br />

somites and the average crown-to-rump length is 2.00<br />

mm. By Day 16, there are 58 to 65 somites and the<br />

crown-to-rump length is about 13.5 mm. At Day 22<br />

– the average date of birth – the crown-to-rump length<br />

ranges from 40.5 to 42.6 mm and the weight of the<br />

neonate is 5.9 to 6.4 grams.<br />

Many factors influence the rate of embryo development,<br />

including the light-dark cycle that affects the onset of<br />

ovulation, the initial position of the embryo in the genital<br />

tract, the hormonal variables of the mother, litter size,<br />

maternal diet and environmental conditions. During<br />

the complex processes of development, toxicological<br />

and environmental factors also can affect the rate of<br />

development. As a result, the actual rate of embryo<br />

development can vary from the nominal gestational age.<br />

11 12 13 14 15 16 17 18 19 20 21 22<br />

Days In Gestation


<strong>Sprague</strong> Dawley ® <strong>Rat</strong> <strong>Model</strong><br />

Production of Timed-Pregnant<br />

<strong>Sprague</strong> Dawley ® <strong>Rat</strong>s at <strong>Taconic</strong><br />

<strong>Taconic</strong> breeding specialists use proven, highly effective<br />

procedures to produce timed-pregnant <strong>Sprague</strong>-<br />

Dawley ® rats. While gestational age cannot be<br />

determined with total precision, strict adherence to<br />

pre-defined mating procedures and close monitoring<br />

of female rats after they are co-housed with males can<br />

define with accuracy the 24-hour period during which<br />

mating and presumably conception occurs.<br />

At <strong>Taconic</strong>, the day of sperm cell detection in females<br />

is called the sperm-positive date and is considered<br />

Day 1 of gestation. After setup the prior day, animal<br />

care technicians take vaginal swabs of females cohoused<br />

with males between 7 and 10 a.m. daily. This<br />

procedure assumes that timed-pregnant females have<br />

mated and conception has occurred from 0 to 24 hours<br />

before the designated sperm-positive date. Presumably,<br />

the majority mate around the midpoint of the previous<br />

day’s dark cycle, from 6 p.m. to 6 a.m.<br />

When investigators order timed-pregnant rats at a<br />

specified developmental age for delivery on a specific<br />

date, <strong>Taconic</strong> technicians select rats based on the<br />

sperm-positive date. For instance, for an order for<br />

rats bearing embryos at Day 15 of gestational age<br />

for delivery on January 15, <strong>Taconic</strong> would select<br />

timed-pregnant females with a sperm-positive date of<br />

January 1. To avoid confusion over conflicting<br />

conventions for defining gestational age,<br />

<strong>Taconic</strong> advises investigators to specify the<br />

sperm-positive date when ordering timedpregnant<br />

<strong>Sprague</strong> Dawley ® rats.<br />

US: 1-888-822-6642 • custserv@taconic.com | Europe: +45 70 23 04 05 • taconiceurope@taconic.com<br />

Since <strong>Taconic</strong>’s method for selecting timed-pregnant<br />

females results in full-term pregnancies approximately<br />

95% of the time, we do not supply extra rats with each<br />

order. However, spontaneous abortions and small litters<br />

of fewer than four pups do occur on occasion. When<br />

expending considerable time and resources to prepare<br />

for a study using timed-pregnant rats on a specific day<br />

– and especially when using a small number of dams<br />

or fetuses – we advise you to order extra timedpregnant<br />

rats.<br />

Reproduction Parameters<br />

of <strong>Sprague</strong> Dawley ® <strong>Rat</strong>s<br />

Male <strong>Rat</strong>s<br />

Age at pairing (mating): 8-10 weeks<br />

Weight at pairing: 250-300 grams<br />

Period of “Economic Reproductive Ability”: 6-9 months<br />

Female <strong>Rat</strong>s<br />

Age at pairing (mating): 8-10 weeks<br />

Weight at pairing: 180-225 grams<br />

Period of “Economic Reproductive Ability”: 6-9 months<br />

Length of estrous cycle: 4-5 days<br />

Duration of estrous: 10-20 hours<br />

Time of ovulation: 8-11 hours after onset of estrous<br />

Gestation<br />

Time of copulation: Near midpoint of previou dark cycle<br />

Time sperm is detected in vagina: Day 1<br />

Time of implantation: Late Day 5<br />

Length of gestation: 21-23 days


Contact Us<br />

Consult with our specialists to discuss your <strong>Sprague</strong> Dawley ® needs:<br />

<strong>Taconic</strong> (US):<br />

1-888-822-6642 or custserv@taconic.com<br />

<strong>Taconic</strong> (Europe):<br />

+45 70 23 04 05 or taconiceurope@taconic.com<br />

References<br />

Beaudoin, A.R. (1980) Embryology and teratology In: The<br />

Laboratory <strong>Rat</strong>, Vol II, Academic Press.<br />

Bernier SG, Lazarus DD, Clark E, Doyle B, Labenski MT,<br />

Thompson CD, Westlin WF, Hannig G. (2004) A methionine<br />

aminopeptidase-2 inhibitor, PPI-2458, for the treatment of<br />

rheumatoid arthritis; Proc Natl Acad Sci, 101(29):<br />

10768-10773.<br />

Blandau, RJ (1943) The fate of the unfertilized ova in the<br />

albino rat. Anat. Rec. 87: 17-27.<br />

Blandau, RJ (1945) The first maturation divisions of the<br />

rat ovum. Anat. Rec. 92: 449-457.<br />

Blandau, RJ and Odor, D.L. (1950) Observations on<br />

fertilization and the first segmentation division in rat ova.<br />

Am J Anat. 89(1): 29-61.<br />

Campbell SE, Gerdes AM (1987) Regional differences in<br />

cardiac myocyte dimensions and number in <strong>Sprague</strong>-Dawley<br />

rats from different suppliers. Proc. Soc. Exper. Biol. Med.<br />

186, 211-217.<br />

Chen XL, Ciren SZ, Zhang H, Duan LG, Wesley A.<br />

(2009) Effect of 5-FU on modulation of disarrangement<br />

of immuneassociated cytokines in experimental acute<br />

pancreatitis. World J Gastroenterol,15(16): 2032-2037.<br />

Chin E, Zhou J, Bondy C. (1993) Anatomical and<br />

Developmental Patterns of Facilitative Glucose Transporter<br />

Gene Expression in the <strong>Rat</strong> Kidney; J Clin Invest, 91:<br />

1810-1815.<br />

Ding Y, Yan Q, Ruan JW, Zhang YQ, Li WJ, Zhang YJ, Li Y,<br />

Dong H, Zeng YS. (2009) Electro-acupuncture promotes<br />

survival, differentiation of the bone marrow mesenchymal<br />

stem cells as well as functional recovery in the spinal cordtransected<br />

rats. BMC Neuroscience, 10: 35.<br />

Enders, A.C. and Schlafke, S. (1967) A morphological<br />

analysis of the early implantation stages in the rat.<br />

Am. J. Anat. 120: 185-226.<br />

US: 1-888-822-6642 • custserv@taconic.com | Europe: +45 70 23 04 05 • taconiceurope@taconic.com<br />

<strong>Sprague</strong> Dawley ® <strong>Rat</strong> <strong>Model</strong><br />

Gear RB, Yan M, Schneider J, Succop P, Heffelfinger SC,<br />

Clegg DJ. Charles River <strong>Sprague</strong> Dawley ® <strong>Rat</strong>s Lack Early<br />

Age-Dependent Susceptibility to DMBA-Induced Mammary<br />

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lactate oxidation by neurons and astroglia in vitro and on<br />

glucose utilization by brain in vivo; Proc Natl Acad Sci,<br />

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Iwamoto J, Matsumoto H, Tadeda T, Sato Y, Yeh J. (2009)<br />

Comparison of the Effect of Vitamin K2 and Risedronate<br />

on Trabecular Bone in Glucocorticoid-Treated <strong>Rat</strong>s: A Bone<br />

Histomorphometry Study. Yonsei Med J, 50(2): 189-194.<br />

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HS, Choi JS, Moon MH, Sung CK. (2009) In Vivo MR Imaging<br />

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<strong>Sprague</strong> Dawley ® <strong>Rat</strong> <strong>Model</strong><br />

Kim JB, Jung JY, Ahn JC, Rhee CK, Hwang HJ. (2009)<br />

Antioxidant and Anti-Apoptotic Effect of Melatonin on the<br />

Vestibular Hair Cells of <strong>Rat</strong> Utricles. Clinical and Experimental<br />

Otorhinolaryngology, 2(1): 6-12.<br />

Lim S, Ahn SY, Song IC Chung MH, Jang HC, Park KS,<br />

Lee KU, Pak YK, Lee HK. (2009) Chronic Exposure to the<br />

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Liu J, Wan R, Xu XF, Wang XP, Yang WJ, Xia YJ, Liu H, Yan<br />

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treatment robustly protects neurons in the central nervous<br />

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Sci, 95(5): 2642-2647.<br />

Porter J, King S, Honeycutt A. (2007) Prenatal high-salt<br />

diet in the <strong>Sprague</strong>-Dawley rat programs blood pressure and<br />

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Rahman S, Oberdorf A, Montecino M, Tanhauser SM, Lian<br />

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Endocrinology, 133: 3050-3053.<br />

Riggs M, Maunsell F, Reyes L, Brown M. (2008)<br />

Hematogenous infection of <strong>Sprague</strong>-Dawley rats with<br />

Mycoplasma pulmonis: development of a model for maternal<br />

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Salcido-Neyoy ME, Sierra-Santoyo A, Beltrán-Ramírez O,<br />

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the detoxification of diethylnitrosamine in rat liver cancer.<br />

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US: 1-888-822-6642 • custserv@taconic.com | Europe: +45 70 23 04 05 • taconiceurope@taconic.com<br />

Scharfman HE, Mercurio TC, Goodman JH, Wilson MA,<br />

MacLusky NJ. (2003) Hippocampal Excitability Increases<br />

during the Estrous Cycle in the <strong>Rat</strong>: A Potential Role for<br />

Brain-Derived Neurotrophic Factor; J Neurosci, 23(37):<br />

11641-11652.<br />

Shansky RM, Rubinow K, Brennan A, Arnsten AFT. (2006)<br />

The effects of sex and hormonal status on restraint-stressinduced<br />

working memory impairment; Behav Brain Funct<br />

2006; 2: 8.<br />

Stoffel EC, Ulibarri CM, Craft RM. (2003) Gonadal steroid<br />

hormone modulation of nociception, morphine antinociception<br />

and reproductive indices in male and female rats; J Pain,<br />

103(3): 285-302.<br />

Stoffel EC, Ulibarri CM, Folk JE, Rice KC, Craft RM. (2005)<br />

Gonadal Hormone Modulation of Mu, Kappa, and Delta Opioid<br />

Antinociception in Male and Female <strong>Rat</strong>s; J Pain, 6(4):<br />

261-274.<br />

Wan J, Ernstgard L, Song BJ, Shoaf SE. (2006)<br />

Chlorzoxazone metabolism is increased in fasted <strong>Sprague</strong>-<br />

Dawley rats; J Pharm Pharmacol, 58(1): 51-61.<br />

Wang Q, Zhang P, Gao HB. (2009) Luteinizing hormone<br />

induces expression of 11beta-hydroxysteroid dehydrogenase<br />

type 2 in rat Leydig cells. Reproductive Biology and<br />

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