1. 2.91.61.92.32.63.14.21.43.61.66.04.13.6 Global KO *: P<0.05 ALP activity

2. Rip-rPerk Perk global ko 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

3. Col1-cre 1.00.71.41.20.9

4. ID genometype DOBSEXslope/2ulage (DAY)BW (g) 15164O+/-P 2-3/2-31/16/2005F1.011531.78 15169O+/-P 2-3/2-31/16/2005M1.411529.36 15170O-/-P 2-3/2-31/16/2005M1.111526.91 15171O+/-P 2-3/2-31/16/2005M1.611528.16 15164AO-/-P 2-3/2-45/4/2005F7.485.54 15164BO+/-P 2-3/2-55/4/2005M5.185.05 15164CO-/-P 2-3/2-65/4/2005M6.285.94 15164DO-/-P 2-3/2-75/4/2005F8.184.9 15164EO-/-P 2-3/2-85/4/2005F8.085.4 15164FO-/-P 2-3/2-95/4/2005F6.785.2 15164GO+/-P 2-3/2-105/4/2005F7.184.77 15164HO-/-P 2-3/2-115/4/2005M6.385.41 15164IO-/-P 2-3/2-125/4/2005F7.184.71 OC-cre

5. SEXAGE slope/2ul 12642AN-P2-3/2-3 147.44 12642BN-P2-3/2-3 148.53 12642CN+P2-3/2-3 148.55 12642DN-P2-3/2-3 1412.32 12642EN-P2-3/2-3 1412.10 15639 N+P2-3/2-3 177.70 15642 N-KO 1713.13 15643 N+P2-3/2-3 178.34 15489 N-P2-3/2-321 9.49 15490 N+P2-3/2-321 8.41 15491 N+P2-3/2-321 9.74 15492 N+P2-3/2-321 8.04 Serum ALP activity NGN3-cre

6. Serum ALP activity SEXAGE slope/2ul 14593 E-P2-3/2-318 8.61 14594 E+P2-3/2-318 7.43 14595 E+P2-3/2-318 8.52 14596 E-P2-3/2-318 9.78 14609 E+P2-3/2-316 10.35 14610 E-P2-3/2-316 8.95 14611 E-P2-3/2-316 9.51 14612 E+P2-3/2-316 9.91 Ela-cre

7. SEXAGE slope/2ul 14211BP+/2-3 413.43 14211CP+/2-3 413.13 14211DP+/2-3 414.17 14211EX+P2-3/2-3 415.12 14211FP+/2-3 413.18 14211GP+/2-3 412.45 14211HX+P+/2-3 418.19 14211JP2-3/2-3 416.10 15651 FX-P+/2-3 186.48 15653 FX-P+/2-3 185.81 15654 FX+P2-3/2-3 186.68 15656 MX+P+/2-3 185.59 14759AX+P+/2-3 287.22 14759BX-P+/2-3 285.67 14759CX-P+/2-3 285.93 14759DX+P2-3/2-3 286.86 14759EX+P+/2-3 286.69 14759FX-P+/2-3 286.31 14759GX-P2-3/2-3 285.31 14759HX-P2-3/2-3 285.49 15444 FX-P+/2-328 5.34 15445 FX-P2-3/2-328 5.64 15446 MX+P2-3/2-328 10.23 15447 MX+P+/2-328 5.27 15448 MX+P+/2-328 4.29 Serum ALP activity PDX-cre

8. 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?

9. Osteocalcin level in serum ng/ul serumaverageKO/WT 8d 15294BWTF342276±941 15294DHTF209 15294EKOF322380±831.4 15294FKOF439 6d 14882ARP+HTM374435±861 14882BRP+HTF497 14882CRP+KOF359366±100.8 14882DRP+KOM373

10. OD405 DOBSEXAGEBWTrFrACPTrACPTrFsACPko/WT 15878EIIAKO3/25/2005M6190.61580.65630.0405 15879EIIAWT3/25/2005M6130.270.52960.60190.07230.529066 15880EIIAHT3/25/2005M6126.440.45340.53420.0808 15899EIIAWT3/30/2005F5621.390.69380.88190.1881 15903EIIAKO3/30/2005M5610.810.62880.77010.14130.751196 16116129KO4/15/2005F4012.280.60090.71250.1116 16117129WT4/15/2005M4024.780.52940.69410.16470.677596 174316241RP+HT4/17/2005F3819.170.6360.75980.1238 174316242RP+KO4/17/2005F3815.290.49630.57250.07621.030949 174316243RP+KO4/17/2005F3816.430.64840.82630.1779 174316245RP+KO4/17/2005M3815.540.6050.74980.1448 174316246RP+HT4/17/2005M3819.230.59120.69740.1062 174316247RP+HT4/17/2005M3823.180.62860.74970.1211 174316248RP+HT4/17/2005M3823.240.68820.8530.1648 176816256RP+WT4/19/2005F3620.330.6740.79820.1242 176816258RP+KO4/19/2005F3614.240.67270.81970.1471.183575 176816256RP+WT4/19/2005F380.91111.11060.1995 176816258RP+KO4/19/2005F380.8030.96780.16480.826065 TRAP5b ACTIVITY

11. GLOBAL ko 1.21.10.91.01.50.40.93.0 Trap ACTIVITY

12. RIP-rPERK Global KO 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

13. COL1 CRE 1.00.71.10.32.71.3

14. Oc-CRE IDgenometypeDOBSEXage (DAY)BW (g)trap activity 15164O+/-P 2-3/2-31/16/2005F11531.78 6 15169O+/-P 2-3/2-31/16/2005M11529.36 4 15170O-/-P 2-3/2-31/16/2005M11526.91 -3 15171O+/-P 2-3/2-31/16/2005M11528.16 2 15164AO-/-P 2-3/2-35/4/2005F85.54 5 15164BO+/-P 2-3/2-35/4/2005M85.05 5 15164CO-/-P 2-3/2-35/4/2005M85.94 6 15164DO-/-P 2-3/2-35/4/2005F84.9 7 15164EO-/-P 2-3/2-35/4/2005F85.4 8 15164FO-/-P 2-3/2-35/4/2005F85.2 6 15164GO+/-P 2-3/2-35/4/2005F84.77 3 15164HO-/-P 2-3/2-35/4/2005M85.41 6 15164IO-/-P 2-3/2-35/4/2005F84.71 8