Reference SummarySundberg JP, PLoS One 2014;9(12):e113582

Title

Immune Status, Strain Background, and Anatomic Site of Inoculation Affect Mouse Papillomavirus (MmuPV1) Induction of Exophytic Papillomas or Endophytic Trichoblastomas.

Authors

Sundberg JP; Stearns TM; Joh J; Proctor M; Ingle A; Silva KA; Dadras SS; Jenson AB; Ghim SJ

Journal

PLoS One

Volume

9

Issue

12

Year

2014

Pages

e113582

Abstract

Papillomaviruses (PVs) induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), was horizontally transmitted within an inbred colony of NMRI-Foxn1nu/Foxn1nu (nude; T cell deficient) mice of an unknown period of time. A ground-up, filtered papilloma inoculum was not capable of infecting C57BL/6J wild-type mice; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1nu and B6.Cg-Foxn1nu, but not NU/J-Foxn1nu, mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, lacking B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail, and condylomas of the vaginal lining which could be induced by separate scarification or simultaneous scarification of MmuPV1 at all four sites. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Although trichoepitheliomas are benign, aggressive tumors, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were highly dysregulated.

Links

J:217142 – MGI References
25474466 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6.Cg-Foxn1nu/J Skin - Dorsal region carcinoma - basal
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

B6.Cg-Foxn1nu/J Skin - Dorsal region carcinoma - basal
  • mouse papillomavirus (MmuPV1)
Adipose tissue

observed

B6.Cg-Foxn1nu/J Skin - Dorsal region carcinoma - poorly differentiated
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

B6.Cg-Foxn1nu/J Skin - Dorsal region lesion
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0 - observed

NU/J Skin - Dorsal region lesion
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0 - observed

B6.Cg-Foxn1nu/J Skin - Dorsal region lesion - malignant
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

Swiss/RVCri-ba Skin - Dorsal region papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

B6.Cg-Foxn1nu/J Skin - Dorsal region papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

B6.Cg-Foxn1nu/J Skin - Dorsal region squamous cell carcinoma
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

C57BL/6J Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0

Swiss/RVCri-ba Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

NU/J Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0

B6.Cg-Foxn1nu/J Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

NMRI-Foxn1nu Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

B6.129S2-Ighmtm1Cgn/J Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0

B6.129S7-Rag1tm1Mom/J Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

B6.CB17-Prkdcscid/SzJ Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

NOD.CB17-Prkdcscid/J Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0

B6.129S2-Cd4tm1Mak/J Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0

B6.129S2-Cd8tm1Mak/J Skin - Dorsal region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0

B6.Cg-Foxn1nu/J Skin - Epidermis hyperplasia
  • mouse papillomavirus (MmuPV1)
Skin - Epidermis

observed

B6.Cg-Foxn1nu/J Skin - Facial region lesion
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

NU/J Skin - Facial region lesion
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

B6.Cg-Foxn1nu/J Skin - Facial region papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

NMRI-Foxn1nu Skin - Facial region papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

B6.129S7-Rag1tm1Mom/J Skin - Facial region papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

B6.CB17-Prkdcscid/SzJ Skin - Facial region papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

C57BL/6J Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

0

NU/J Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

0

B6.Cg-Foxn1nu/J Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

NMRI-Foxn1nu Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

B6.129S2-Ighmtm1Cgn/J Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

0

B6.129S7-Rag1tm1Mom/J Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

B6.CB17-Prkdcscid/SzJ Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

observed

NOD.CB17-Prkdcscid/J Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

0

B6.129S2-Cd4tm1Mak/J Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

0

B6.129S2-Cd8tm1Mak/J Skin - Facial region tumor
  • mouse papillomavirus (MmuPV1)
Skin - Facial region

0

B6.Cg-Foxn1nu/J Skin - Hair follicle trichoblastoma
  • mouse papillomavirus (MmuPV1)
Skin - Hair follicle

observed

NMRI-Foxn1nu Skin - Hair follicle trichoblastoma
  • mouse papillomavirus (MmuPV1)
Skin - Hair follicle

observed

B6.129S7-Rag1tm1Mom/J Skin - Hair follicle trichoblastoma
  • mouse papillomavirus (MmuPV1)
Skin - Hair follicle

observed

B6.CB17-Prkdcscid/SzJ Skin - Hair follicle trichoblastoma
  • mouse papillomavirus (MmuPV1)
Skin - Hair follicle

observed

B6.Cg-Foxn1nu/J Skin - Hair follicle trichoblastoma
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

observed

B6.Cg-Foxn1nu/J Skin - Head papilloma - exophytic
  • mouse papillomavirus (MmuPV1)
Muzzle

observed

B6.Cg-Foxn1nu/J Skin - Tail lesion - epithelial
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

B6.Cg-Foxn1nu/J Skin - Tail papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

NMRI-Foxn1nu Skin - Tail papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

B6.129S7-Rag1tm1Mom/J Skin - Tail papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

NU/J Skin - Tail papilloma
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

NMRI-Foxn1nu Skin - Tail papilloma - exophytic
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

B6.Cg-Foxn1nu/J Skin - Tail papilloma - exophytic
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

C57BL/6J Skin - Tail tumor
  • mouse papillomavirus (MmuPV1)
Skin - Tail

0

B6.Cg-Foxn1nu/J Skin - Tail tumor
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

NMRI-Foxn1nu Skin - Tail tumor
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

B6.129S2-Ighmtm1Cgn/J Skin - Tail tumor
  • mouse papillomavirus (MmuPV1)
Skin - Tail

0

B6.129S7-Rag1tm1Mom/J Skin - Tail tumor
  • mouse papillomavirus (MmuPV1)
Skin - Tail

observed

NOD.CB17-Prkdcscid/J Skin - Tail tumor
  • mouse papillomavirus (MmuPV1)
Skin - Tail

0

B6.129S2-Cd4tm1Mak/J Skin - Tail tumor
  • mouse papillomavirus (MmuPV1)
Skin - Tail

0

B6.129S2-Cd8tm1Mak/J Skin - Tail tumor
  • mouse papillomavirus (MmuPV1)
Skin - Tail

0

B6.Cg-Foxn1nu/J Skin gland - Sebaceous gland lesion
  • mouse papillomavirus (MmuPV1)
Skin - Dorsal region

0

B6.Cg-Foxn1nu/J Skin hyperplasia
  • mouse papillomavirus (MmuPV1)
Skin

observed

C57BL/6J Skin lesion
  • mouse papillomavirus (MmuPV1)
Skin

0

NMRI-Foxn1nu Skin papilloma
  • mouse papillomavirus (MmuPV1)
Neck

observed

NMRI-Foxn1nu Skin papilloma
  • mouse papillomavirus (MmuPV1)
Leg

observed

B6.Cg-Foxn1nu/J Skin papilloma - exophytic
  • mouse papillomavirus (MmuPV1)
Skin

observed

B6.Cg-Foxn1nu/J Vagina hyperplasia - mucosal
  • mouse papillomavirus (MmuPV1)
Vagina

observed