Reference SummaryAntoch MP, Cell Cycle 2013 Dec 1;12(23):3673-80

Title

Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis.

Authors

Antoch MP; Toshkov I; Kuropatwinski KK; Jackson M

Journal

Cell Cycle

Volume

12

Issue

23

Year

2013

Pages

3673-80

Abstract

There is a growing body of evidence that components of the circadian clock are involved in modulation of numerous signaling pathways, and that clock deregulation due to environmental or genetic factors contributes to the development of various pathologies, including cancer. Previous work performed in tissue culture and in in vivo mouse models defined mammalian PERIOD proteins as tumor suppressors, although some experimental inconsistencies (the use of mice on mixed genetic background, lack of sexual discrimination) did not allow a definitive conclusion. To address this issue in a systematic way, we performed a detailed analysis comparing the incidence of tumor development after low-dose ionizing radiation in male and female wild-type, Per1(-/-), and Per2(-/-) mice. We showed that in contrast to previous reports deficiency in either Per1 or Per2 genes by itself does not make mice more tumor-prone; moreover, some of the long-term effects of ionizing radiation in Per2-deficient mice are reminiscent more of accelerated aging rather than tumor-prone phenotype. Our histopathological analysis also revealed significant sexual dimorphism both in the rate of radiation-induced tumorigenesis and in the spectrum of tumors developed, which underscores the importance of using sex-matched experimental groups for in vivo studies. Based on our results, we suggest that the role of PER proteins as bona fide tumor suppressors needs to be reevaluated.

Links

J:223430 – MGI References
24091726 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.129S4-Per1tm1Drw These mice were backcrossed 12 generations onto a C57BL/6J genetic background and subsequently maintained by homozygous matings.
B6.129S4-Per2tm1Drw These mice were backcrossed 12 generations onto a C57BL/6J genetic background and subsequently maintained by homozygous matings.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J Blood vessel hemangiosarcoma Blood vessel

0

C57BL/6J Blood vessel hemangiosarcoma
  • cesium-137
Blood vessel

0

B6.129S4-Per1tm1Drw Blood vessel hemangiosarcoma Blood vessel

0

B6.129S4-Per1tm1Drw Blood vessel hemangiosarcoma
  • cesium-137
Blood vessel

0

B6.129S4-Per1tm1Drw Blood vessel hemangiosarcoma
  • cesium-137
Spleen

6.25

B6.129S4-Per2tm1Drw Blood vessel hemangiosarcoma Blood vessel

0

B6.129S4-Per2tm1Drw Blood vessel hemangiosarcoma
  • cesium-137
Blood vessel

0

C57BL/6J Leukocyte leukemia Leukocyte

0

C57BL/6J Leukocyte leukemia
  • cesium-137
Leukocyte

0

B6.129S4-Per1tm1Drw Leukocyte leukemia Leukocyte

0

B6.129S4-Per1tm1Drw Leukocyte leukemia
  • cesium-137
Leukocyte

0 - 7.7

B6.129S4-Per2tm1Drw Leukocyte leukemia Leukocyte

0

B6.129S4-Per2tm1Drw Leukocyte leukemia
  • cesium-137
Leukocyte

0

C57BL/6J Leukocyte lymphoma Leukocyte

0

C57BL/6J Leukocyte lymphoma
  • cesium-137
Leukocyte

5.3 - 21

B6.129S4-Per1tm1Drw Leukocyte lymphoma Leukocyte

0 - 12.5

B6.129S4-Per1tm1Drw Leukocyte lymphoma
  • cesium-137
Leukocyte

0 - 15

B6.129S4-Per1tm1Drw Leukocyte lymphoma
  • cesium-137
Thymus

observed

B6.129S4-Per2tm1Drw Leukocyte lymphoma Leukocyte

0 - 6.7

B6.129S4-Per2tm1Drw Leukocyte lymphoma
  • cesium-137
Leukocyte

0 - 8.3

C57BL/6J Leukocyte lymphoma - lymphosarcoma Leukocyte

0

C57BL/6J Leukocyte lymphoma - lymphosarcoma
  • cesium-137
Leukocyte

0 - 5.3

B6.129S4-Per1tm1Drw Leukocyte lymphoma - lymphosarcoma Leukocyte

0 - 12.5

B6.129S4-Per1tm1Drw Leukocyte lymphoma - lymphosarcoma
  • cesium-137
Leukocyte

0 - 6.25

B6.129S4-Per2tm1Drw Leukocyte lymphoma - lymphosarcoma Leukocyte

0

B6.129S4-Per2tm1Drw Leukocyte lymphoma - lymphosarcoma
  • cesium-137
Leukocyte

0

B6.129S4-Per2tm1Drw Liver - Bile duct cystadenoma
  • cesium-137
Liver - Bile duct

7.7

C57BL/6J Liver cystadenoma Liver

0

C57BL/6J Liver cystadenoma
  • cesium-137
Liver

0 - 14

B6.129S4-Per1tm1Drw Liver cystadenoma Liver

0

B6.129S4-Per1tm1Drw Liver cystadenoma
  • cesium-137
Liver

0

B6.129S4-Per2tm1Drw Liver cystadenoma Liver

0

B6.129S4-Per2tm1Drw Liver cystadenoma
  • cesium-137
Liver

8.3

B6.129S4-Per2tm1Drw Liver hepatoma
  • cesium-137
Liver

observed

C57BL/6J Ovary - Granulosa cell tumor Ovary - Granulosa cell

0

C57BL/6J Ovary - Granulosa cell tumor
  • cesium-137
Ovary - Granulosa cell

5.3

B6.129S4-Per1tm1Drw Ovary - Granulosa cell tumor Ovary - Granulosa cell

0

B6.129S4-Per1tm1Drw Ovary - Granulosa cell tumor
  • cesium-137
Ovary - Granulosa cell

37.5

B6.129S4-Per2tm1Drw Ovary - Granulosa cell tumor Ovary - Granulosa cell

0

B6.129S4-Per2tm1Drw Ovary - Granulosa cell tumor
  • cesium-137
Ovary - Granulosa cell

15

C57BL/6J Ovary cystadenoma Ovary

0

C57BL/6J Ovary cystadenoma
  • cesium-137
Ovary

42

B6.129S4-Per1tm1Drw Ovary cystadenoma Ovary

0

B6.129S4-Per1tm1Drw Ovary cystadenoma
  • cesium-137
Ovary

25

B6.129S4-Per2tm1Drw Ovary cystadenoma Ovary

0

B6.129S4-Per2tm1Drw Ovary cystadenoma
  • cesium-137
Ovary

0

C57BL/6J Ovary tumor Ovary

0

C57BL/6J Ovary tumor
  • cesium-137
Ovary

47

B6.129S4-Per1tm1Drw Ovary tumor Ovary

0

B6.129S4-Per1tm1Drw Ovary tumor
  • cesium-137
Ovary

62.5

B6.129S4-Per2tm1Drw Ovary tumor Ovary

0

B6.129S4-Per2tm1Drw Ovary tumor
  • cesium-137
Ovary

15

C57BL/6J (Unspecified organ) tumor (Unspecified organ)

0

C57BL/6J (Unspecified organ) tumor
  • cesium-137
(Unspecified organ)

36 - 58

B6.129S4-Per1tm1Drw (Unspecified organ) tumor (Unspecified organ)

0 - 25

B6.129S4-Per1tm1Drw (Unspecified organ) tumor
  • cesium-137
(Unspecified organ)

23 - 62.5

B6.129S4-Per2tm1Drw (Unspecified organ) tumor (Unspecified organ)

0 - 6.7

B6.129S4-Per2tm1Drw (Unspecified organ) tumor
  • cesium-137
(Unspecified organ)

17 - 23