Reference SummaryTumiati M, J Pathol 2015 Jan;235(1):136-46

Title

 Loss of Rad51c accelerates tumourigenesis in sebaceous glands of Trp53-mutant mice.

Authors

 Tumiati M; Hemmes A; Uusivirta S; Koopal S; Kankainen M; Lehtonen E; Kuznetsov SG

Journal

 J Pathol

Volume

 235

Issue

 1

Year

 2015

Pages

 136-46

Abstract

 Germline mutations in RAD51C predispose to breast and ovarian cancers. However, the mechanism of RAD51C-mediated carcinogenesis is poorly understood. We previously reported a first-generation Rad51c-knock-out mouse model, in which a spontaneous loss of both Rad51c and Trp53 together resulted in a high incidence of sebaceous carcinomas, particularly in preputial glands. Here we describe a second-generation mouse model, in which Rad51c is deleted, alone or together with Trp53, in sebaceous glands, using Cre-mediated recombination. We demonstrate that deletion of Rad51c alone is not sufficient to drive tumourigenesis and may only cause keratinization of preputial sebocytes. However, deletion of Rad51c together with Trp53 leads to tumour development at around 6 months of age, compared to 11 months for single Trp53-mutant mice. Preputial glands of double-mutant mice are also characterized by increased levels of cell proliferation and DNA damage and form multiple hyperplasias, detectable as early as 2 months of age. Our results reveal a critical synergy between Rad51c and Trp53 in tumour progression and provide a predictable in vivo model system for studying mechanisms of Rad51c-mediated carcinogenesis. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Links

 J:216440 – MGI References
25270124 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C57BL/6J Possible gentoypes for control mice: Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+; Krt14 +/+ Rad51ctm1Sks; Krt14 +/+ Rad51ctm1Sks/+ Trp53tm1Brn; or Krt14 +/+ Rad51ctm1Sks Trp53tm1Brn.
These mice were either lacking the cre knock-in or were heterozygous for the conditional allele(s).

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Ear - Zymbal gland carcinoma in situ Ear - Zymbal gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Ear - Zymbal gland carcinoma in situ Ear - Zymbal gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Ear - Zymbal gland carcinoma in situ Ear - Zymbal gland

2.9
C57BL/6J Ear - Zymbal gland carcinoma in situ Ear - Zymbal gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Ear - Zymbal gland squamous cell carcinoma Ear - Zymbal gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Ear - Zymbal gland squamous cell carcinoma Ear - Zymbal gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Ear - Zymbal gland squamous cell carcinoma Ear - Zymbal gland

20.6
C57BL/6J Ear - Zymbal gland squamous cell carcinoma Ear - Zymbal gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Eye - Meibomian gland carcinoma in situ Eye - Meibomian gland

observed
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Eye - Meibomian gland squamous cell carcinoma Eye - Meibomian gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Eye - Meibomian gland squamous cell carcinoma Eye - Meibomian gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Eye - Meibomian gland squamous cell carcinoma Eye - Meibomian gland

14.7
C57BL/6J Eye - Meibomian gland squamous cell carcinoma Eye - Meibomian gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Mammary gland carcinoma Mammary gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Mammary gland carcinoma Mammary gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Mammary gland carcinoma Mammary gland

2.9
C57BL/6J Mammary gland carcinoma Mammary gland

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Muzzle carcinoma - sebaceous Muzzle

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Muzzle carcinoma - sebaceous Muzzle

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Muzzle carcinoma - sebaceous Muzzle

8.8
C57BL/6J Muzzle carcinoma - sebaceous Muzzle

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Oral cavity squamous cell carcinoma Oral cavity

observed
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Preputial gland (male) carcinoma in situ Preputial gland (male)

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Preputial gland (male) carcinoma in situ Preputial gland (male)

0 - 5.3
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Preputial gland (male) carcinoma in situ Preputial gland (male)

0 - 76.5
C57BL/6J Preputial gland (male) carcinoma in situ Preputial gland (male)

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Preputial gland (male) dysplasia Preputial gland (male)

observed
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Preputial gland (male) hyperplasia Preputial gland (male)

0 - 25
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Preputial gland (male) hyperplasia Preputial gland (male)

15.8 - 40
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Preputial gland (male) hyperplasia Preputial gland (male)

0 - 100
C57BL/6J Preputial gland (male) hyperplasia Preputial gland (male)

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Preputial gland (male) metaplasia Preputial gland (male)

observed
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Preputial gland (male) metaplasia Preputial gland (male)

observed
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Preputial gland (male) squamous cell carcinoma Preputial gland (male)

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Preputial gland (male) squamous cell carcinoma Preputial gland (male)

10.5
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Preputial gland (male) squamous cell carcinoma Preputial gland (male)

17.6
C57BL/6J Preputial gland (male) squamous cell carcinoma Preputial gland (male)

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Skin lesion - benign Skin

3.8
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Skin lesion - benign Skin

5.3
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Skin lesion - benign Skin

29.4
C57BL/6J Skin lesion - benign Skin

9.5
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Skin papilloma Skin

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Skin papilloma Skin

5.3
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Skin papilloma Skin

8.8
C57BL/6J Skin papilloma Skin

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Skin squamous cell carcinoma Skin

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn Skin squamous cell carcinoma Skin

5.3
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn Skin squamous cell carcinoma Skin

70.6
C57BL/6J Skin squamous cell carcinoma Skin

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks (Unspecified organ) tumor (Unspecified organ)

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks/+ Trp53tm1Brn (Unspecified organ) tumor (Unspecified organ)

15.8 - 29
C57BL/6J-Rad51ctm1Sks/+ Trp53tm1Brn (Unspecified organ) tumor (Unspecified organ)

0
C57BL/6J-Krt14tm1.1(cre)Wbm/+ Rad51ctm1Sks Trp53tm1Brn (Unspecified organ) tumor (Unspecified organ)

100
C57BL/6J-Rad51ctm1Sks Trp53tm1Brn (Unspecified organ) tumor (Unspecified organ)

0
C57BL/6J (Unspecified organ) tumor (Unspecified organ)

0