Reference SummaryBrayton CF, Vet Pathol 2012 Jan;49(1):85-105

Title

Pathobiology of aging mice and GEM: background strains and experimental design.

Authors

Brayton CF; Treuting PM; Ward JM

Journal

Vet Pathol

Volume

49

Issue

1

Year

2012

Pages

85-105

Abstract

The use of induced and spontaneous mutant mice and genetically engineered mice (and combinations thereof) to study cancers and other aging phenotypes to advance improved functional human life spans will involve studies of aging mice. Genetic background contributes to pathology phenotypes and to causes of death as well as to longevity. Increased recognition of expected phenotypes, experimental variables that influence phenotypes and research outcomes, and experimental design options and rationales can maximize the utility of genetically engineered mice (GEM) models to translational research on aging. This review aims to provide resources to enhance the design and practice of chronic and longevity studies involving GEM. C57BL6, 129, and FVB/N strains are emphasized because of their widespread use in the generation of knockout, transgenic, and conditional mutant GEM. Resources are included also for pathology of other inbred strain families, including A, AKR, BALB/c, C3H, C57L, C58, CBA, DBA, GR, NOD.scid, SAMP, and SJL/J, and non-inbred mice, including 4WC, AB6F1, Ames dwarf, B6, 129, B6C3F1, BALB/c,129, Het3, nude, SENCAR, and several Swiss stocks. Experimental strategies for long-term cross-sectional and longitudinal studies to assess causes of or contributors to death, disease burden, spectrum of pathology phenotypes, longevity, and functional healthy life spans (health spans) are compared and discussed.

Links

J:235854 – Mouse Genome Informatics
22215684 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
(C57BL/6 x C3H)F1 Adrenal gland - Cortex lesion Adrenal gland - Cortex

observed

BALB/cAnNBdf Adrenal gland - Cortex tumor Adrenal gland - Cortex

observed

FVB/NTac Adrenal gland - Medulla pheochromocytoma Adrenal gland - Medulla

observed

BALB/cStCrlfC3Hf/Nctr Adrenal gland - Subcapsular cell hyperplasia - spindle cell Adrenal gland - Subcapsular cell

observed

(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Adrenal gland hyperplasia Adrenal gland

observed

NMRI Adrenal gland tumor Adrenal gland

observed

BALB/cStCrlfC3Hf/Nctr Blood tumor Blood

observed

C57BL/6JfC3Hf/Nctr Blood tumor Blood

observed

[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Blood tumor Blood

43 - 55

B6;129 Blood tumor Blood

observed

B6;129 Blood vessel hemangioma Blood vessel

observed

C;129P2 Blood vessel hemangioma Blood vessel

observed

C57BL/6 Blood vessel hemangiosarcoma Blood vessel

observed

B6;129 Blood vessel hemangiosarcoma Blood vessel

observed

(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Blood vessel hemangiosarcoma Blood vessel

observed

C57BL/6JNia Blood vessel neoplasm Blood vessel

0 - 8

C57BL/6J Blood vessel neoplasm Blood vessel

2 - 4

B6;129S4 Blood vessel neoplasm Blood vessel

0 - 10

B6;129 Blood vessel neoplasm Blood vessel

9

129S4/SvJae Blood vessel neoplasm Blood vessel

0 - 12.9

C57BL/6JNia Bone neoplasm Bone

0 - 2

C57BL/6J Bone neoplasm Bone

0 - 2

B6;129S4 Bone neoplasm Bone

0

129S4/SvJae Bone neoplasm Bone

0

BALB/cStCrlfC3Hf/Nctr Eye - Harderian gland adenoma Eye - Harderian gland

observed

FVB/NTac Eye - Harderian gland adenoma - acidophilic Eye - Harderian gland

observed

C57BL/6JNia Eye - Harderian gland neoplasm Eye - Harderian gland

0

C57BL/6J Eye - Harderian gland neoplasm Eye - Harderian gland

0

B6;129S4 Eye - Harderian gland neoplasm Eye - Harderian gland

0 - 4

B6;129 Eye - Harderian gland neoplasm Eye - Harderian gland

0

129S4/SvJae Eye - Harderian gland neoplasm Eye - Harderian gland

0 - 53.9

129S4/SvJae Eye - Harderian gland tumor Eye - Harderian gland

observed

BALB/cAnNBdf Eye - Harderian gland tumor Eye - Harderian gland

observed

NMRI Eye - Harderian gland tumor Eye - Harderian gland

observed

C57BL/6JNia Intestine neoplasm Intestine

0 - 4

C57BL/6J Intestine neoplasm Intestine

0 - 4

B6;129S4 Intestine neoplasm Intestine

4

129S4/SvJae Intestine neoplasm Intestine

2.3 - 2.6

SENCAR Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell lymphoma Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell

observed

C57L Leukocyte - Lymphocyte - B-lymphocyte lymphoma Leukocyte - Lymphocyte - B-lymphocyte

observed

SJL/J Leukocyte - Lymphocyte - B-lymphocyte lymphoma Leukocyte - Lymphocyte - B-lymphocyte

observed

CFW Leukocyte - Lymphocyte - B-lymphocyte lymphoma Leukocyte - Lymphocyte - B-lymphocyte

observed

SAMP Leukocyte - Lymphocyte - B-lymphocyte lymphoma - immunoblastic Leukocyte - Lymphocyte - B-lymphocyte

observed

SJL/J Leukocyte - Lymphocyte - Pre-B-lymphocyte lymphoma Leukocyte - Lymphocyte - Pre-B-lymphocyte

observed

NOD.CB17-Prkdcscid/J Leukocyte - Lymphocyte - Pro-T-lymphocyte lymphoma Leukocyte - Lymphocyte - Pro-T-lymphocyte

observed

AKR/J Leukocyte - Lymphocyte - T-lymphocyte lymphoma Leukocyte - Lymphocyte - T-lymphocyte

observed

C58/J Leukocyte - Lymphocyte - T-lymphocyte lymphoma Leukocyte - Lymphocyte - T-lymphocyte

observed

C.B-17-Prkdcscid Leukocyte - Lymphocyte - T-lymphocyte lymphoma Thymus

observed

SJL/J Leukocyte - Lymphocyte lymphoma - Hodgkin Leukocyte - Lymphocyte

observed

CD-1 Leukocyte - Lymphocyte lymphoma - lymphocytic Leukocyte - Lymphocyte

observed

C57BL/6JNia Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

observed - 15.4

C57BL/6J Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

observed - 15

B6;129S4 Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

6

129S4/SvJae Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

0 - 4.2

C57BL/6NNia Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

observed

FVB/NTac Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

observed

FVB/NHsd Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

observed

SAMP Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

observed

SENCAR Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

observed

AKR/J Leukocyte leukemia Leukocyte

observed

C58 Leukocyte leukemia Leukocyte

observed

C58/J Leukocyte leukemia Leukocyte

observed

SJL/J Leukocyte leukemia Leukocyte

observed

[not specified]-Foxn1nu Leukocyte leukemia Leukocyte

observed

C57BL/6JNia Leukocyte lymphoma Leukocyte

observed - 50

C57BL/6J Leukocyte lymphoma Leukocyte

observed - 57

B6;129S4 Leukocyte lymphoma Leukocyte

observed - 67

129S4/SvJae Leukocyte lymphoma Leukocyte

2.5 - 6.3

AKR Leukocyte lymphoma Leukocyte

observed

BALB/cStCrlfC3Hf/Nctr Leukocyte lymphoma Leukocyte

observed

C57BL/6N Leukocyte lymphoma Leukocyte

observed

C57BL/6NNia Leukocyte lymphoma Leukocyte

observed

FVB/NTac Leukocyte lymphoma Leukocyte

observed

NOD/ShiLt Leukocyte lymphoma Leukocyte

observed

NOD.129S-Rag2tm1Fwa Leukocyte lymphoma Leukocyte

observed

[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte lymphoma Leukocyte

observed

(Af x C57BL/6)F1 Leukocyte lymphoma Leukocyte

observed

(C57BL/6 x C3H/HeN)F1 Leukocyte lymphoma Leukocyte

observed

(C57BL/6 x C3H)F1 Leukocyte lymphoma
  • (see notes regarding diet)
Leukocyte

observed

(C57BL/6 x C3H)F1 Leukocyte lymphoma Leukocyte

observed

C;129P2 Leukocyte lymphoma Leukocyte

observed

(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Leukocyte lymphoma Leukocyte

observed

[not specified]-Foxn1nu Leukocyte lymphoma Leukocyte

observed

CD-1 Leukocyte lymphoma Leukocyte

observed

C58 Leukocyte lymphoma - lymphosarcoma Leukocyte

observed

CD-1 Leukocyte lymphoma - pleomorphic Leukocyte

observed

BALB/cStCrlfC3Hf/Nctr Liver - Hepatocyte neoplasm Liver - Hepatocyte

observed

FVB/NTac Liver - Hepatocyte tumor Liver - Hepatocyte

observed

(C57BL/6 x C3H/HeN)F1 Liver adenoma Liver

observed

(C57BL/6 x C3H)F1 Liver adenoma Liver

observed

(C57BL/6 x C3H/HeN)F1 Liver carcinoma Liver

observed

(C57BL/6 x C3H)F1 Liver carcinoma Liver

observed

B6;129S4 Liver hepatocellular adenoma Liver

observed

SENCAR Liver hepatocellular adenoma Liver

observed

CD-1 Liver hepatocellular adenoma Liver

observed

B6;129 Liver hepatocellular carcinoma Liver

observed

B6;129S4 Liver hepatocellular carcinoma Liver

observed

C;129P2 Liver hepatocellular carcinoma Liver

observed

CD-1 Liver hepatocellular carcinoma Liver

observed

C3H Liver hepatoma Liver

observed

CBA Liver hepatoma Liver

observed

CBA/Birmingham Liver hepatoma Liver

observed

(C57BL/6 x C3H)F1 Liver hepatoma
  • (see notes regarding diet)
Liver

observed

C57BL/6JNia Liver neoplasm Liver

1.9 - 6

C57BL/6J Liver neoplasm Liver

0 - 4

B6;129S4 Liver neoplasm Liver

0 - 16

B6;129 Liver neoplasm Liver

9

129S4/SvJae Liver neoplasm Liver

0 - 22.5

129S4/SvJae Liver tumor Liver

observed

C3H/HeJ Liver tumor Liver

observed

C57BR/cdJ Liver tumor Liver

observed

NMRI Liver tumor Liver

observed

B6;129S4 Lung - Alveolus - Type II cell adenoma Lung - Alveolus - Type II cell

observed

B6;129S4 Lung - Alveolus - Type II cell carcinoma Lung - Alveolus - Type II cell

observed

[not specified]-Prop1df Lung adenocarcinoma Lung

observed

[not specified]-Prop1df/+ Lung adenocarcinoma Lung

observed

C;129P2 Lung adenocarcinoma Lung

observed

CD-1 Lung adenocarcinoma Lung

observed

A/HeN Lung adenoma Lung

observed

(C57BL/6 x C3H/HeN)F1 Lung adenoma Lung

observed

(C57BL/6 x C3H)F1 Lung adenoma
  • (see notes regarding diet)
Lung

observed

SENCAR Lung adenoma Lung

observed

CD-1 Lung adenoma Lung

observed

A Lung carcinoma Lung

observed

A/HeN Lung carcinoma Lung

observed

B6;129 Lung carcinoma Lung

observed

(C57BL/6 x C3H/HeN)F1 Lung carcinoma Lung

observed

(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Lung carcinoma Lung

observed

SENCAR Lung carcinoma Lung

observed

C57BL/6JNia Lung neoplasm Lung

0 - 3.8

C57BL/6J Lung neoplasm Lung

2 - 8

B6;129S4 Lung neoplasm Lung

0 - 32

B6;129 Lung neoplasm Lung

17

129S4/SvJae Lung neoplasm Lung

4 - 62.5

FVB/NTac Lung neoplasm Lung

observed

(Af x C57BL/6)F1 Lung neoplasm Lung

observed

129S4/SvJae Lung tumor Lung

observed

A/J Lung tumor Lung

observed

A/HeJ Lung tumor Lung

observed

BALB/c Lung tumor Lung

observed

BALB/cStCrlfC3Hf/Nctr Lung tumor Lung

observed

BALB/cAnNBdf Lung tumor Lung

observed

BALB/cAnNIcr Lung tumor Lung

observed

FVB/NTac Lung tumor Lung

observed

FVB/NHsd Lung tumor Lung

observed

CD-1 Lung tumor Lung

observed

NMRI Lung tumor Lung

observed

CD-1 Mammary gland adenocarcinoma Mammary gland

observed

C3H/HeJ Mammary gland adenocarcinoma - type B
  • MMTV - mouse mammary tumor virus
Mammary gland

observed

C3HeB/FeJ Mammary gland adenocarcinoma - type B Mammary gland

observed

A Mammary gland carcinoma
  • MMTV - mouse mammary tumor virus
Mammary gland

observed

Af Mammary gland carcinoma Mammary gland

observed

C3H Mammary gland carcinoma
  • MMTV - mouse mammary tumor virus
Mammary gland

observed

C3Hf Mammary gland carcinoma Mammary gland

observed

GRS Mammary gland carcinoma Mammary gland

observed

FVB/N Mammary gland hyperplasia Mammary gland

observed

FVB/NCr Mammary gland hyperplasia Mammary gland

observed

C3H/HeJ Mammary gland hyperplasia - alveolar
  • MMTV - mouse mammary tumor virus
Mammary gland

observed

C3HeB/FeJ Mammary gland hyperplasia - alveolar Mammary gland

observed

C57BL/6JNia Mammary gland neoplasm Mammary gland

0 - 2.1

C57BL/6J Mammary gland neoplasm Mammary gland

0

B6;129S4 Mammary gland neoplasm Mammary gland

0

129S4/SvJae Mammary gland neoplasm Mammary gland

0

BALB/cAnNBdf Mammary gland tumor Mammary gland

observed

C3H/HeJ Mammary gland tumor
  • MMTV - mouse mammary tumor virus
Mammary gland

observed

C3HeB/FeJ Mammary gland tumor Mammary gland

observed

C3H/HeN Mammary gland tumor
  • MMTV - mouse mammary tumor virus
Mammary gland

observed

C3H/HeNIcr Mammary gland tumor Mammary gland

observed

C3H/HeNIcrfC57BL Mammary gland tumor Mammary gland

observed

C3H/He Mammary gland tumor
  • MMTV - mouse mammary tumor virus
Mammary gland

observed

C3H/Hef Mammary gland tumor Mammary gland

observed

DBA Mammary gland tumor
  • MMTV - mouse mammary tumor virus
Mammary gland

observed

DBAf Mammary gland tumor Mammary gland

observed

DBA/2AnIcr Mammary gland tumor Mammary gland

observed

FVB/NTac Mammary gland tumor Mammary gland

observed

SENCAR Mammary gland tumor Mammary gland

observed

FVB/NTac Neuroectoderm - Neural crest cell tumor Subcutis

observed

BALB/cStCrlfC3Hf/Nctr Ovary cyst Ovary

observed

C57BL/6JfC3Hf/Nctr Ovary cyst Ovary

observed

SAMP Ovary cyst Ovary

observed

C57BL/6JNia Ovary neoplasm Ovary

1.9

C57BL/6J Ovary neoplasm Ovary

1

B6;129S4 Ovary neoplasm Ovary

17

129S4/SvJae Ovary neoplasm Ovary

26.7

FVB/NTac Ovary tumor Ovary

observed

FVB/NHsd Ovary tumor Ovary

observed

B6;129S4 Ovary tumor Ovary

observed

B6;129S4 Pancreas - Islet of Langerhans hyperplasia Pancreas - Islet of Langerhans

observed

(C57BL/6 x C3H)F1 Pancreas - Islet of Langerhans hyperplasia
  • (see notes regarding diet)
Pancreas - Islet of Langerhans

observed

C57BL/6JNia Pancreas neoplasm Pancreas

0

C57BL/6J Pancreas neoplasm Pancreas

0

B6;129S4 Pancreas neoplasm Pancreas

0 - 4

129S4/SvJae Pancreas neoplasm Pancreas

0 - 2.1

FVB/NCr Pituitary gland - Pars distalis hyperplasia Pituitary gland - Pars distalis

observed

C57BL/6JfC3Hf/Nctr Pituitary gland adenoma Pituitary gland

observed

C57BL/6JNia Pituitary gland adenoma Pituitary gland

observed

C57BL/6NNia Pituitary gland adenoma Pituitary gland

observed

FVB/NTac Pituitary gland adenoma Pituitary gland

observed

FVB/NHsd Pituitary gland adenoma Pituitary gland

observed

FVB/NCr Pituitary gland adenoma Pituitary gland

observed

(C57BL/6 x C3H/HeN)F1 Pituitary gland adenoma Pituitary gland

observed

(C57BL/6 x C3H)F1 Pituitary gland adenoma
  • (see notes regarding diet)
Pituitary gland

observed

(C57BL/6 x C3H)F1 Pituitary gland adenoma Pituitary gland

observed

(C57BL/6 x C3H/HeN)F1 Pituitary gland carcinoma Pituitary gland

observed

(C57BL/6 x C3H)F1 Pituitary gland carcinoma Pituitary gland

observed

C57BL/6JfC3Hf/Nctr Pituitary gland cyst Pituitary gland

observed

C57BL/6JNia Pituitary gland neoplasm Pituitary gland

0 - 25.5

C57BL/6J Pituitary gland neoplasm Pituitary gland

0 - 7

B6;129S4 Pituitary gland neoplasm Pituitary gland

0 - 2

B6;129 Pituitary gland neoplasm Pituitary gland

15

129S4/SvJae Pituitary gland neoplasm Pituitary gland

0

FVB/NTac Pituitary gland prolactinoma Pituitary gland

observed

C57BL/6J Pituitary gland tumor Pituitary gland

observed

NMRI Pituitary gland tumor Pituitary gland

observed

FVB/N Skin - Ear squamous cell carcinoma
  • ear tag
Skin - Ear

observed

CBA/Birmingham Spleen hyperplasia Spleen

observed

(C57BL/6 x C3H/HeN)F1 Subcutis neoplasm Subcutis

observed

129/Sv Testis teratocarcinoma Testis

observed

129/Sv Testis teratoma Testis

observed

AKR Thymus leukemia Thymus

observed

AKR Thymus lymphoma Thymus

observed

AKR/J Thymus lymphoma Thymus

observed

NOD.CB17-Prkdcscid Thymus lymphoma Thymus

observed

B6;129S4 Thyroid gland - Follicular cell adenoma Thyroid gland - Follicular cell

observed

B6;129S4 Thyroid gland - Follicular cell carcinoma Thyroid gland - Follicular cell

observed

(C57BL/6 x C3H)F1 Thyroid gland cyst
  • (see notes regarding diet)
Thyroid gland

observed

C57BL/6JNia Thyroid gland neoplasm Thyroid gland

0

C57BL/6J Thyroid gland neoplasm Thyroid gland

0

B6;129S4 Thyroid gland neoplasm Thyroid gland

2 - 8

129S4/SvJae Thyroid gland neoplasm Thyroid gland

0 - 4.2

(C57BL/6 x C3H)F1 Uterus - Endometrium cyst
  • (see notes regarding diet)
Uterus - Endometrium

observed

(BALB/cByJ x C57BL/6J)F1 x (C3H/HeJ x DBA/2J)F1 Uterus - Endometrium hyperplasia Uterus - Endometrium

observed

C57BL/6JfC3Hf/Nctr Uterus - Endometrium hyperplasia - cystic Uterus - Endometrium

observed

B6;129S4 Uterus - Endometrium tumor Uterus - Endometrium

observed

C3H/HeJ Uterus hyperplasia - glandular
  • MMTV - mouse mammary tumor virus
Uterus

observed

C3HeB/FeJ Uterus hyperplasia - glandular Uterus

observed

C57BL/6JNia Uterus neoplasm Uterus

3.8

C57BL/6J Uterus neoplasm Uterus

4

B6;129S4 Uterus neoplasm Uterus

8

129S4/SvJae Uterus neoplasm Uterus

20.8

BALB/cStCrlfC3Hf/Nctr Uterus polyp Uterus

observed

C57BL/6JfC3Hf/Nctr (Unspecified organ) angiosarcoma (Unspecified organ)

observed

C57BL/6JNia (Unspecified organ) neoplasm (Unspecified organ)

57 - 71

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

35 - 50

B6;129S4 (Unspecified organ) neoplasm (Unspecified organ)

25 - 60

B6;129 (Unspecified organ) neoplasm (Unspecified organ)

49 - 80

129S4/SvJae (Unspecified organ) neoplasm (Unspecified organ)

0 - 35

C57L (Unspecified organ) reticulum cell neoplasm (Unspecified organ)

observed

BALB/cStCrlfC3Hf/Nctr (Unspecified organ) reticulum cell sarcoma (Unspecified organ)

observed

BALB/cAnNBdf (Unspecified organ) reticulum cell sarcoma (Unspecified organ)

observed

SJL/J (Unspecified organ) reticulum cell sarcoma (Unspecified organ)

observed

NMRI (Unspecified organ) tumor (Unspecified organ)

observed