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`
`charles river
`
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`
`C57BL/6 Mice
`NOMENCLATURE: C57BL/6NCrl
`
`Strain Origin
`Developed by C.C. Little in 1921 from a mating of Miss Abbie Lathrop's stock that also gave rise to strains C57BR
`and C57l. Strains 6 and 10 separated about 1937. To The Jackson Laboratory from Hall in 1948. To NIH in 1951
`from The Jackson Laboratory at F32. To Charles River in 1974 from NIH.
`
`Coat Color: Black
`Produced: North America, Europe and Japan
`
`Pharmacosmos, Exh. 1060, p. 1
`
`

`
`C57BL/6 Mice
`NOMENCLATURE: C57BU6NCrl
`Genetic Management of C57BU6 Mouse Colony
`Inbred strains are defined as animals produced by a minimum of 20 generations of brother-sister mating,
`traceable to a single founding pair. Charles River uses our International Genetic Standardization (IGS) program
`coupled with a pyramid mating system designed to maintain authenticity and the highest possible levels of
`genetic uniformity. The pyramid mating system (see Figure 1) ensures that our C57BL/6 colonies are genetically
`identical within each strain (i.e., fundamentally free of genetic differences that could increase variation in
`experimental results). In this system, the foundation colony serves as the genetic and health standard and
`provides breeders for the top level of the pyramid in every barrier room. This top level, the nucleus colony,
`is composed of a relatively small number of pedigreed brother-sister mating pairs that produce breeders for
`the next level of the pyramid, in addition to replenishing itself. In larger colonies, the next level is called the
`expansion colony, and it provides breeders to the production colony, which in turn produces the animals that are
`commercially available. The unidirectional flow of breed stock in this system helps to ensure that any genetic
`changes or mutations, which would be most likely to occur in the more populous expansion or production
`colonies than in the smaller nucleus colony, will "wash out" within a single generation. Nucleus colonies are
`replaced every three to five years (within 1 O generations) by migrating new breed stock from the foundation
`colony to the barrier rooms. As a safeguard against any large scale disaster affecting the foundation colonies
`of several strains, Charles River has cryopreserved a sufficient number of embryos for multiple, complete
`replacements of those populations. For further information regarding Charles River's IGS program, please refer
`to the IGS Technical Sheet found at www.criver.com/info/rm.
`
`Figure 1: Pyramid Mating System
`
`Isolators
`
`Barrier Rooms
`
`Gnotobiotic Isolator Maintained
`Foundation Nucleus Colony (B XS)
`
`~~~ Pedigree Nucleus Colony (BX S)
`
`Production Colony
`(Random Mating)
`
`Inbred Strains Available For Research
`
`Pharmacosmos, Exh. 1060, p. 2
`
`

`
`Charles River C57BU6 Data
`
`Clinical Chemistry
`C57BL/6NCrl*
`
`Male
`
`Female
`
`Mean
`S.D.
`n
`Mean
`S.D.
`n
`
`ALB
`(g/dl)
`3.24
`0.46
`110
`3.33
`0.62
`92
`
`ALK
`(U/I)
`195.49
`55.56
`114
`234.51
`93.36
`96
`
`CHOL
`(mg/di)
`112.17
`23.59
`118
`102.00
`24.76
`101
`
`ALT
`(U/I)
`66.46
`184.87
`108
`50.53
`37.15
`95
`
`GLU
`(ma/dll
`247.00
`60.86
`114
`236.78
`55.17
`94
`
`AST
`(U/I)
`127.58
`142.05
`114
`126.54
`133.29
`98
`
`p
`(ma/dll
`10.66
`2.05
`116
`10.03
`1.98
`96
`
`TBIL
`(mg/di)
`0.32
`0.28
`111
`0.28
`0.10
`94
`
`K+
`(meQ/ll
`9.65
`0.89
`45
`16.48
`27.99
`13
`
`BUN
`(mg/di)
`14.34
`5.26
`113
`13.83
`6.60
`94
`
`Na
`(meQ/I)
`158.44
`10.53
`45
`144.01
`40.43
`13
`
`Ca
`(mg/di)
`11.00
`1.06
`113
`10.93
`1.68
`92
`
`TP
`(Q/dl)
`5.67
`0.76
`113
`5.57
`0.95
`95
`
`CL
`(meqJI)
`117.95
`6.16
`45
`120.43
`10.29
`13
`
`TRIG
`(ma/dll
`153.38
`56.20
`117
`151.13
`52.97
`102
`
`Screening Period: August 2006 to November 2007
`Euthanasia: CO 2
`Bleed Route: Cardiac puncture after euthanasia
`Analyzing Equipment: Alfa Wassermann Ace Afera
`
`GGT
`(LJ/I)
`3.71
`2.58
`59
`2.59
`2.19
`39
`
`C57BL/6NCrl*
`
`Male
`
`Female
`
`CRE
`(ma/dll
`0.33
`Mean
`0.12
`S.D.
`102
`n
`Mean
`0.31
`S.D.
`0.08
`85
`n
`*North American colonies only/non-tasted values
`+ Potassium levels reflect acidosis caused by CO, euthanasia
`Age: 56 - 70 days
`Diet: Purina 5L79 rodent chow
`Temperature: 68 - 72°F
`Humidity: 40 - 60%
`
`Hematology
`
`C57BL/6NCrl*
`
`Male
`
`Female
`
`Mean
`S.D.
`n
`Mean
`S.D.
`n
`
`wee
`(KfµI)
`8.91
`2.50
`109
`8.69
`2.44
`113
`
`C57BL/6NCrl*
`
`Male
`
`Female
`
`PLT
`IK/ul)
`1350.67
`Mean
`S.D.
`337.98
`n
`101
`1167.12
`Mean
`306.96
`S.D.
`105
`n
`*North American colonies only/non-fasted values
`
`Age: 56 - 70 days
`Diet: Purina 5L79 rodent chow
`Temperature: 68 - 72°F
`Humidity: 40 - 60%
`
`ROW
`(%)
`17.89
`1.15
`107
`17.90
`1.24
`111
`
`RBC
`(M/µI)
`9.51
`1.25
`107
`9.17
`1.05
`111
`
`MPV
`(fl)
`5.04
`0.44
`101
`4.90
`0.33
`105
`
`HGB
`(g/dl)
`14.33
`2.64
`107
`13.72
`1.59
`111
`
`NEUT
`(K/JJI)
`1.45
`1.01
`109
`1.22
`0.51
`113
`
`HCT
`(%)
`47.02
`7.27
`107
`45.32
`6.27
`111
`
`LYMPH
`IK/ul)
`6.85
`1.97
`109
`6.92
`1.92
`113
`
`MCV
`(fl)
`49.44
`3.95
`107
`49.46
`3.88
`111
`
`MONO
`(K/JJI)
`0.43
`0.24
`109
`0.37
`0.15
`113
`
`MCH
`foal
`14.88
`1.03
`107
`15.02
`1.11
`110
`
`EOS
`IK/ul)
`0.14
`0.12
`109
`0.16
`0.13
`113
`
`MCHC
`(g/dl)
`30.28
`3.04
`107
`30.54
`3.19
`111
`
`BASO
`(K/JJI)
`0.03
`0.03
`109
`0.03
`0.04
`113
`
`Screening Period: August 2006 to November 2007
`Euthanasia: CO 2
`Bleed Route: Cardiac puncture after euthanasia
`Analyzing Equipment: Drew Scientific HemaVet
`
`Pharmacosmos, Exh. 1060, p. 3
`
`

`
`Strain Highlights
`
`50
`
`I
`
`I
`
`I
`
`I
`
`I
`
`MEAN WEIGHT +/-1 STANDARD DE'MllON
`
`N Strain
`• Enhanced ES cell growth and morphology vs. J substrains
`{Pettitt, S.J. et al. 2009)
`• Lower incidence of vaginal septa vs. J substrains (Gearhart, S. et al. 2004)
`• Lower genetic variability among the N substrains vs. J substrains
`(Zurita, E. et al. 2010)
`• Does not carry the Nnt deletion (Freeman, H.C. et al. 2006)
`NCrl (Charles River)
`• Global availability through more than 20 breeding facilities
`• Bred worldwide under the Charles River International Genetic
`Standardization (IGS) program
`• VAF® Plus and VAF Elite® health status
`
`_
`
`,
`
`II
`
`MALE
`
`'
`
`~
`
`I
`
`I
`
`I
`FEMALE
`
`10
`
`I'/
`
`0
`3
`
`11
`
`13
`
`15
`
`AGE IN WEEKS
`
`Research Applications and References
`
`The C57BLJ6 mouse is a multipurpose model that can be used in such fields as model creation, physiology, safety
`and efficacy and genetics.
`
`General Purpose
`- Atochina, E.N. et al. Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein
`(SP)-D production following allergic sensitization. Respiratory Research, 4: 15 (2003).
`- Crabbe, J.C. et al. Genetics of mouse behavior: interactions with laboratory environment. Science, 284, 1670-1672 (1999).
`- Freeman, H.C. et a/_ Deletion of micotinamide nucleotide transhydrogenase: A new quantitative trait locus accounting for glucose
`intolerance in C57BU6J mice. Diabetes, 55(7): 2153-2156 (2006).
`- Hu. C.C. et al. Diet-induced changes in stearoyl-CoA sesaturase 1 expression in obesity-prone and -resistant mice. Obesity Research,
`12(8): 1264-1270 (2004).
`- Regner, U. C., Avner, P. Congenic mice: cutting tools for complex immune disorders. Nature Reviews-lmmunolof!f, 3(3): 243-252 (2003).
`
`Physiology
`- Bryant, C.D. et al. Behavioral differences among C57BL/6 substrains: implications for transgtenic and knockout studies.
`J_ Neurogenetics, 22(4): 315-331 (2008).
`- Gearhart, S. et al. Increased incidence of vaginal septum in C57BL/6J mice since 1976. Comparative Medicine, 54(4): 418-421 (2004).
`- Toye, A.A et a/_ A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia, 48(4):
`675-686 (2005).
`
`Model Creation/Genetics
`- Hanson, G.W. et a/_ Large-scale gene trapping in C57BU6N mouse embryonic stem cells. Genome Research, 18(1 O): 1679-1679
`(2008)_
`- Pettitt, S.J. et al. Agouti C57BU6N embryonic stem cells for mouse genetic resources. Nature Methods, 6(7): 493-495 (2009).
`- Watkins-Chow, D.E., Pavan, W.J. Genomic copy number and expression variation within the C57BU6J inbred mouse strain. Genome
`Research, 18{1): 60-66 (2008).
`- Zurita, E. et al. Genetic polymorphisms among C57BU6 mouse inbred strains. Transgenic Research. [Epub], (2010).
`
`~
`
`charles river I r.....ardl
`
`model•
`
`North America: 1.877.CRIVER.1 (1.&n.274.8371)
`Europe, A91a, RoW: +800.3195.3430 • +1.781.222.7800
`emall: Hkc:harleertver@crl.com • -.crlYer.com
`C 2011, Chfllles Riller Lmxlratories International, Inc.
`
`Pharmacosmos, Exh. 1060, p. 4