Reference SummaryChrisp CE, Vet Pathol 1996 Nov;33(6):735-43

Title

 Lifespan and lesions in genetically heterogeneous (four-way cross) mice: a new model for aging research.

Authors

 Chrisp CE; Turke P; Luciano A; Swalwell S; Peterson J; Miller RA

Journal

 Vet Pathol

Volume

 33

Issue

 6

Year

 1996

Pages

 735-43

Abstract

 Genetically heterogeneous animal models provide many advantages for research on aging but have been used infrequently. We present here lifespan and lesion data from a study of mice bred as a cross between (AKR/J x DBA/2J)F1 females and (C57BL/6J x SJL/J)F1 males. In such a four-way cross population, each mouse is genetically unique, but replicate populations of essentially similar genetic structure can be generated quickly, at low cost, and of arbitrary size from commercially available, genetically stable hybrid parents. We employed a protocol in which mice judged to be severely ill were euthanatized to obtain tissue in optimal condition for necropsy, and we were able to infer a likely cause of illness in 42 of 44 animals. Malignant lymphoma, including at least four histopathologically distinct subtypes, was the most common cause and was also a frequent incidental finding in mice dying of other causes. Neoplastic disease, benign or malignant, was the sole or a contributing cause of illness in 90% of the mice for which a cause could plausibly be assigned. A wide range of lethal and nonlethal degenerative lesions was also noted. The coefficient of variation for lifespan in these genetically heterogeneous mice was 26%, similar to that seen in analyses of recombinant inbred mouse lines. Baseline lifespan and pathology data on four-way cross mice is a useful prelude to the exploitation of this rodent model in tests of genetic and mechanistic hypotheses about aging.

Links

 J:37980 – MGI References
8952040 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Adrenal gland - Capsule hyperplasia Adrenal gland - Capsule

0 - 4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Adrenal gland - Medulla pheochromocytoma - malignant Adrenal gland - Medulla

0 - 4.8
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Blood vessel hemangiosarcoma Blood vessel

0
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Blood vessel hemangiosarcoma Liver

2.3 - 4.8
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Blood vessel hemangiosarcoma Lymph node - Mesenteric

2.3 - 4.8
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Bone osteoma Bone - Skull

2.3 - 4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Bone osteoma Bone

0
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte - Lymphoblast lymphoma - lymphoblastic Leukocyte - Lymphoblast

19 - 32
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell lymphoma - follicular Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell

9.1 - 33
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte - Lymphocyte - B-lymphocyte lymphoma - immunoblastic Leukocyte - Lymphocyte - B-lymphocyte

4.8 - 9.1
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte - Lymphocyte lymphoma - small lymphocytic Leukocyte - Lymphocyte

9.1 - 19
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte - Monocyte - Macrophage - Kupffer cell histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Kupffer cell

0 - 4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte - Myelocyte (Granulocyte) - Basophil - Mast cell tumor - malignant Leukocyte - Myelocyte (Granulocyte) - Basophil - Mast cell

0
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte - Myelocyte (Granulocyte) - Basophil - Mast cell tumor - malignant Heart

2.3 - 4.8
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic Leukocyte - Myelocyte (Granulocyte)

4.5 - 4.8
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Leukocyte lymphoma Leukocyte

43 - 67
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Liver cyst Liver

0 - 4.8
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Liver hepatocellular adenoma Liver

0 - 4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Liver hepatocellular carcinoma Liver

0 - 9.1
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Lung adenocarcinoma Lung

0 - 14
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Lung adenoma Lung

0 - 14
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Mammary gland adenocarcinoma Mammary gland

0 - 14
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Muscle - Striated - Skeletal rhabdomyosarcoma Muscle - Striated - Skeletal

0 - 4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] PNS - Schwann cell neurofibrosarcoma PNS - Nerve - Brachial plexus

2.3 - 4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] PNS - Schwann cell neurofibrosarcoma PNS - Schwann cell

0
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Pancreas - Islet of Langerhans adenoma Pancreas - Islet of Langerhans

0 - 4.8
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Pituitary gland adenoma Pituitary gland

0 - 24
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Prostate gland hyperplasia Prostate gland

4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Thyroid gland - Medulla - C cell hyperplasia Thyroid gland - Medulla - C cell

0 - 4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Thyroid gland adenoma Thyroid gland

0 - 4.5
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Tooth - Tooth enamel organ dysplasia Tooth - Tooth enamel organ

19 - 50
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Uterus - Endometrium - Stroma polyp Uterus - Endometrium - Stroma

4.8
[(AKR/J x DBA/2J)F1] x [(C57BL/6J x SJL/J)F1] Uterus - Endometrium hyperplasia Uterus - Endometrium

4.8