4. 7

13. 5

7. 8

12. 7

5. 5

10. 6

7. 6

17. 6

5. 0

13. 3

3. 9

12. 2

3. 5

14. 6

4. 05. 5

4. 0

14. 3

3. 25. 0

2. 1

12. 7

2. 6

10. 5

1. 3

4. 8

0. 0

5. 0

10. 0

15. 0

20. 0

25. 0

30. 0

WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO

P2 P3 P5* P7* P8* P16 P21* P26 P40 P41 P46 P61* P667

2.9 1.6 1.9 2.3 2.6 3.1 4.2 1.4 3.6 1.6 6.0 4.1 3.6

Global KO

*: P<0.05

ALP activity

Rip-rPerk Perk global ko

14. 04

11. 64

6. 3

11. 5

5. 8

9. 1

10. 6 11. 0

9. 6

6. 2

8. 5

10. 5

4. 25. 0

3. 64. 3

2. 83. 6

5. 0

10. 9

2. 7 2. 53. 0

3. 6

2. 5 2. 5 2. 4

8. 1

0. 00

2. 00

4. 00

6. 00

8. 00

10. 00

12. 00

14. 00

16. 00

18. 00

20. 00

WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO

P4h P6 P23 P25 P36 P38 P51 P58 P62 P64 P203 P214 P321 P386

0.8 1.8 1.6 1.0 0.6 1.2 1.2 1.2 1.3 2.2 0.9 1.2 1.0 3.4

Col1-cre

5. 2 5. 3

7. 8

5. 4

2. 23. 0 3. 4 3. 9

1. 0 0. 9 0. 6 0. 6

0. 01. 02. 03. 04. 05. 06. 07. 08. 09. 0

10. 0

WT KO WT KO WT KO WT KO WT KO WT KO

P24 P25 P26 P39 P106 P129

1.0 0.7 1.4 1.2 0.9 0.9

ID genometype DOB SEX slope/2ul age (DAY) BW (g)

15164 O+/- P 2-3/2-3 1/16/2005 F 1.0 115 31.78

15169 O+/- P 2-3/2-3 1/16/2005 M 1.4 115 29.36

15170 O-/- P 2-3/2-3 1/16/2005 M 1.1 115 26.91

15171 O+/- P 2-3/2-3 1/16/2005 M 1.6 115 28.16

15164A O-/- P 2-3/2-4 5/4/2005 F 7.4 8 5.54

15164B O+/- P 2-3/2-5 5/4/2005 M 5.1 8 5.05

15164C O-/- P 2-3/2-6 5/4/2005 M 6.2 8 5.94

15164D O-/- P 2-3/2-7 5/4/2005 F 8.1 8 4.9

15164E O-/- P 2-3/2-8 5/4/2005 F 8.0 8 5.4

15164F O-/- P 2-3/2-9 5/4/2005 F 6.7 8 5.2

15164G O+/- P 2-3/2-10 5/4/2005 F 7.1 8 4.77

15164H O-/- P 2-3/2-11 5/4/2005 M 6.3 8 5.41

15164I O-/- P 2-3/2-12 5/4/2005 F 7.1 8 4.71

OC-cre

SEX AGE slope/2ul

12642A N- P2-3/2-3 14 7.44

12642B N- P2-3/2-3 14 8.53

12642C N+ P2-3/2-3 14 8.55

12642D N- P2-3/2-3 14 12.32

12642E N- P2-3/2-3 14 12.10

15639 N+ P2-3/2-3 17 7.70

15642 N- KO 17 13.13

15643 N+ P2-3/2-3 17 8.34

15489 N- P2-3/2-3 21 9.49

15490 N+ P2-3/2-3 21 8.41

15491 N+ P2-3/2-3 21 9.74

15492 N+ P2-3/2-3 21 8.04

Serum ALP activity

NGN3-cre

Serum ALP activity

SEX AGE slope/2ul

14593 E- P2-3/2-3 18 8.61

14594 E+ P2-3/2-3 18 7.43

14595 E+ P2-3/2-3 18 8.52

14596 E- P2-3/2-3 18 9.78

14609 E+ P2-3/2-3 16 10.35

14610 E- P2-3/2-3 16 8.95

14611 E- P2-3/2-3 16 9.51

14612 E+ P2-3/2-3 16 9.91

Ela-cre

SEX AGE slope/2ul

14211B P+/2-3 4 13.43

14211C P+/2-3 4 13.13

14211D P+/2-3 4 14.17

14211E X+ P2-3/2-3 4 15.12

14211F P+/2-3 4 13.18

14211G P+/2-3 4 12.45

14211H X+ P+/2-3 4 18.19

14211J P2-3/2-3 4 16.10 15651 F X- P+/2-3 18 6.48 15653 F X- P+/2-3 18 5.81 15654 F X+ P2-3/2-3 18 6.68 15656 M X+ P+/2-3 18 5.59

14759A X+ P+/2-3 28 7.22

14759B X- P+/2-3 28 5.67

14759C X- P+/2-3 28 5.93

14759D X+ P2-3/2-3 28 6.86

14759E X+ P+/2-3 28 6.69

14759F X- P+/2-3 28 6.31

14759G X- P2-3/2-3 28 5.31

14759H X- P2-3/2-3 28 5.49

15444 F X- P+/2-3 28 5.34 15445 F X- P2-3/2-3 28 5.64 15446 M X+ P2-3/2-3 28 10.23 15447 M X+ P+/2-3 28 5.27 15448 M X+ P+/2-3 28 4.29

Serum ALP activityPDX-cre

What causes ALP level elevated? What does this imply?

1. Very high levels of ALP can be caused by liver disorders, such as hepatitis, blockage of the bile ducts (obstructive jaundice), gallstones, cirrhosis, liver cancer, or cancer that has spread (metastasized) to the liver from another location in the body.

2. High ALP levels can be caused by bone diseases, such as Paget's disease, osteomalacia, rickets, bone tumors, or by overactive parathyroid glands (hyperparathyroidism). Normal healing of a bone fracture can also raise ALP levels.

3. Heart failure, heart attack, mononucleosis or kidney cancer can raise ALP levels. A serious infection that has spread throughout the body (sepsis) can also raise ALP levels.

Liver? Or Bone?

Osteocalcin level in serum

ng/ul serum average KO/WT

8d

15294B WT F 342 276±94 1

15294D HT F 209

15294E KO F 322 380±83 1.4

15294F KO F 439

6d

14882A RP+HT M 374 435±86 1

14882B RP+HT F 497

14882C RP+KO F 359 366±10 0.8

14882D RP+KO M 373

OD405

DOB SEX AGE BW TrFrACP TrACP TrFsACP ko/WT

15878 EIIA KO 3/25/2005 M 61 9 0.6158 0.6563 0.0405

15879 EIIA WT 3/25/2005 M 61 30.27 0.5296 0.6019 0.0723 0.529066

15880 EIIA HT 3/25/2005 M 61 26.44 0.4534 0.5342 0.0808

15899 EIIA WT 3/30/2005 F 56 21.39 0.6938 0.8819 0.1881

15903 EIIA KO 3/30/2005 M 56 10.81 0.6288 0.7701 0.1413 0.751196

16116 129 KO 4/15/2005 F 40 12.28 0.6009 0.7125 0.1116

16117 129 WT 4/15/2005 M 40 24.78 0.5294 0.6941 0.1647 0.677596

1743 16241 RP+ HT 4/17/2005 F 38 19.17 0.636 0.7598 0.1238

1743 16242 RP+ KO 4/17/2005 F 38 15.29 0.4963 0.5725 0.0762 1.030949

1743 16243 RP+ KO 4/17/2005 F 38 16.43 0.6484 0.8263 0.1779

1743 16245 RP+ KO 4/17/2005 M 38 15.54 0.605 0.7498 0.1448

1743 16246 RP+ HT 4/17/2005 M 38 19.23 0.5912 0.6974 0.1062

1743 16247 RP+ HT 4/17/2005 M 38 23.18 0.6286 0.7497 0.1211

1743 16248 RP+ HT 4/17/2005 M 38 23.24 0.6882 0.853 0.1648

1768 16256 RP+ WT 4/19/2005 F 36 20.33 0.674 0.7982 0.1242

1768 16258 RP+ KO 4/19/2005 F 36 14.24 0.6727 0.8197 0.147 1.183575

1768 16256 RP+ WT 4/19/2005 F 38 0.9111 1.1106 0.1995

1768 16258 RP+ KO 4/19/2005 F 38 0.803 0.9678 0.1648 0.826065

TRAP5b ACTIVITY

GLOBAL ko

2. 5 3. 0

6. 5 7. 0

9. 0 8. 3

13. 5 13. 0

9. 5

14. 0 14. 0

5. 0

7. 4 6. 7

1

3

0. 0

2. 04. 0

6. 08. 0

10. 0

12. 014. 0

16. 018. 0

20. 0

WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO

P5 P7 P8 P16 P21 P40 P61 P667

1.2 1.1 0.9 1.0 1.5 0.4 0.9 3.0

Trap ACTIVITY

RIP-rPERK Global KO

4. 67

2. 00

6. 0 6. 0

9

8

11. 5

5. 0

8

77. 6

6. 86. 0

9. 0

10

6 6. 0

2. 5

5. 0

8. 7

4

3

2

3

4. 04. 5

4

6

0. 00

2. 00

4. 00

6. 00

8. 00

10. 00

12. 00

14. 00

16. 00

WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO WT KO

P4h P6 P23 P25* P36 P38 P51 P58 P62* P64 P203 P214 P321 P386

0.4 1.0 0.9 0.4 0.9 0.9 1.5 0.6 0.4 1.7 0.8 1.5 1.1 1.5

*: P<0.05

COL1 CRE

7. 3 7. 0 7. 5

5. 0

910

6

2 1. 5

4. 0

2. 0 2. 7

0. 0

2. 0

4. 0

6. 0

8. 0

10. 0

12. 0

WT KO WT KO WT KO WT KO WT KO WT KO

P24 P25 P26 P39 P106 P129

1.0 0.7 1.1 0.3 2.7 1.3

Oc-CRE

ID genometype DOB SEX age (DAY) BW (g) trap activity

15164 O+/- P 2-3/2-3 1/16/2005 F 115 31.78 6

15169 O+/- P 2-3/2-3 1/16/2005 M 115 29.36 4

15170 O-/- P 2-3/2-3 1/16/2005 M 115 26.91 -3

15171 O+/- P 2-3/2-3 1/16/2005 M 115 28.16 2

15164A O-/- P 2-3/2-3 5/4/2005 F 8 5.54 5

15164B O+/- P 2-3/2-3 5/4/2005 M 8 5.05 5

15164C O-/- P 2-3/2-3 5/4/2005 M 8 5.94 6

15164D O-/- P 2-3/2-3 5/4/2005 F 8 4.9 7

15164E O-/- P 2-3/2-3 5/4/2005 F 8 5.4 8

15164F O-/- P 2-3/2-3 5/4/2005 F 8 5.2 6

15164G O+/- P 2-3/2-3 5/4/2005 F 8 4.77 3

15164H O-/- P 2-3/2-3 5/4/2005 M 8 5.41 6

15164I O-/- P 2-3/2-3 5/4/2005 F 8 4.71 8