Type: Inbred Strain;

Additional information on Inbred Strains.

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Mating System: Sibling x Sibling         (Female x Male)   01-MAR-06

Breeding Considerations: This strain is a good breeder.

Species: laboratory mouse

H2 Haplotype: a

Generation:

Generation Definitions

 

Appearance

albino
Related Genotype: a/a Tyrp1b/Tyrp1b Tyrc/Tyrc

Important Note

This strain is homozygous for Cdh23^ahl, the age related hearing loss 1 mutation, and ahl4, which on this background result in progressive hearing loss with onset between three and five months of age.

Description

Developed by LC Strong in 1921 from a cross between a Cold Spring Harbor albino and a Bagg albino, the A/J inbred strain is widely used in cancer and immunology research. It is highly susceptible to cortisone-induced congenital cleft palate. It has a high incidence of spontaneous lung adenomas, and lung tumors readily develop in response to carcinogens. A high percentage of mammary adenocarcinomas (a large proportion of acinar-type) develop in multiparous females. Rare spontaneous myoepitheliomas arising from myoepithelial cells of various exocrine glands have been observed in The Jackson Laboratory substrains.

A/J mice fed an atherogenic diet (1.25% cholesterol, 0.5% cholic acid, and 15% fat) fail to develop atherosclerotic aortic lesions in contrast to several highly susceptible strains of mice (e.g. C57BL/6J, Stock No. 000664; C57L/J, Stock No. 000668, C57BR/cdJ, Stock No. 000667, and SM/J, Stock No. 000687). In addition to atherosclerosis resistance, A/J mice are resistant to diabetes, obesity, insulin resistance and glucose intolerance. On either chow or high fat diet, A/J mice maintain low glucose and insulin levels.

A/J mice develop cigarette smoke-induced emphysema in approximately half the time when compared with C57BL/6J mice. Structural lung damage caused by induced asthma mimics the phenotype found in asthma patients more closely than does the induced damage in BALB/c mice.

A strain characteristic of A/J is a late onset (four to five months) progressive muscular dystrophy as a result of a homozygous retrotransposon insertion in the dysferlin (Dysf) gene. Myofibers in Dysf^prmd homozygotes undergo degeneration and regeneration, and their nuclei are placed centrally. Proximal muscles are more severely affected than distal muscles (Ho M, et al. 2004).

Sequencing of the mitochondrial genome of A/J reveals 10 adenines in a polymorphic adenine repeat sequence in the mt-Tr sequence. This repeat contains nine adenines in NOD/ShiLtJ, A/HeJ, A/WySnJ, and SKH2/J and 10 adenines in A/J, and NZB/B1NJ, and likely enhances the hearing loss associated with the Cdh23^ahl allele (Johnson et al. 2001).

 

Additional Web Information

Sequence data is available from the Mouse Genomes Project at the Wellcome Trust Sanger Institute

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Phenotypic Data

Mouse Phenome Database
Festing Inbred Strain Characteristics: A/J

Mammalian Phenotype Terms provided by MGI

Dysfprmd/Dysfprm

behavior/neurological phenotype

• abnormal physical strength

(MGI Ref ID J:92838)

• limb grasping
  • hind-limb clasping develops after 8 months of age

(MGI Ref ID J:92838)

• inability to spread legs when suspended by their tails after 8 months of age

(MGI Ref ID J:92838)

cellular phenotype

• skeletal muscle fiber necrosis
  • increased numbers of necrotic and regenerating fibers with time

(MGI Ref ID J:92838)

muscle phenotype

• abnormal skeletal muscle fiber morphology
  • abnormalities primarily in proximal muscles at early ages

(MGI Ref ID J:92838)

• hypertrophic fibers, fiber splitting and fat replacement also seen

(MGI Ref ID J:92838)

• abnormal skeletal muscle morphology
  • eventually, active myopathy was seen in all skeletal muscles

(MGI Ref ID J:92838)

• perivascular infiltrates and inflammation seen by 8 months of age

(MGI Ref ID J:92838)

• centrally nucleated skeletal muscle fibers

(MGI Ref ID J:92838)

• skeletal muscle endomysial fibrosis
  • endomysial fibrosis at later stages

(MGI Ref ID J:92838)

• skeletal muscle fiber degeneration
  • fibers with scattered degenerating and regenerating fibers by 4-5 months of age

(MGI Ref ID J:92838)

• skeletal muscle fiber necrosis
  • increased numbers of necrotic and regenerating fibers with time

(MGI Ref ID J:92838)

Il3ram1/Il3ram1

hematopoietic system phenotype

• abnormal common myeloid progenitor cell morphology
  • CFU-GM assays using bone marrow derived cells yield very few colonies in repsonse to interleukin 3, but normal colony growth occurs in response to GM-CSF

(MGI Ref ID J:24918)

• abnormal leukopoiesis
  • Il3 alone does not support granulocyte/macrophage colony formation in bone marrow cells from A/J mice but does in bone marrow from C57BL/6 controls; costimulation with both Il3 and SCF increases the number of colonies formed compared to SCF alone

(MGI Ref ID J:23971)

immune system phenotype

• abnormal leukopoiesis
  • Il3 alone does not support granulocyte/macrophage colony formation in bone marrow cells from A/J mice but does in bone marrow from C57BL/6 controls; costimulation with both Il3 and SCF increases the number of colonies formed compared to SCF alone

(MGI Ref ID J:23971)

Naip5Lgn1-s/Naip5Lgn1-s

immune system phenotype

• increased susceptibility to bacterial infection
  • peritoneal macrophages derived from A/J mice are susceptible to Legionella pneumophilia infection; infected macrophages show a 10-fold increase in bacterial burden after 1 day of infection compared to resistant controls (C57BL/6J)

(MGI Ref ID J:20633)

Csahl4/Csahl4

hearing/vestibular/ear phenotype

• impaired hearing

(MGI Ref ID J:139222)

• increased or absent threshold for auditory brainstem response
  • in A/J mice ABR thresholds at 16 and 32 kHz are elevated by 25 days of age and by 3 months of age the ABR thresholds are more than 50 dB above normal

(MGI Ref ID J:139222)

• increased susceptibility to age-related hearing loss
  • in A/J mice onset of hearing loss is found as early as 25 days of age and is much more severe at 6 months of age than that found in C57BL/6J

(MGI Ref ID J:139222)

Cdh23ahl/Cdh23ahl mt-Trm1

either: A/J X (A/J x CAST/Ei)F1 or A/J X (CAST/Ei x A/J)F1

hearing/vestibular/ear phenotype

• increased or absent threshold for auditory brainstem response
  • average ABR threshold is significantly increased by 3 months of age

(MGI Ref ID J:67312)

• increased susceptibility to age-related hearing loss
  • the presence of this mitochondrial sequence polymorphism in mice homozygous for the ahl allele results in age related hearing loss by 3 months of age, which is absent when the CAST/Ei mitochondrial sequence is instead present

(MGI Ref ID J:67312)

Nrg3ska/Nrg3ska

endocrine/exocrine gland phenotype

• abnormal mammary gland development
  • Background Sensitivity – 95% of female A/J mice display an altered pattern of mammary gland development compared with C57BL/6 which showed no abnormalities in this study

(MGI Ref ID J:60708)

• abnormal mammary gland pattern
  • 95% of females have abnormal mammary gland development

(MGI Ref ID J:60708)

• abnormal nipple development

(MGI Ref ID J:60708)

• absent mammary gland
  • 55% of females observed have this phenotype

(MGI Ref ID J:60708)

• Background Sensitivity – when observed involves only glands of pair #3

(MGI Ref ID J:60708)

• ectopic mammary gland
  • 29% of females observed had this phenotype

(MGI Ref ID J:60708)

• misplacement is usually observed with gland #3

(MGI Ref ID J:60708)

• ectopic nipples

(MGI Ref ID J:60708)

• increased mammary gland number
  • 31% of the females observed have this phenotype or supernumerary nipples

(MGI Ref ID J:60708)

• occasionally found between glands #2 and #4 or below #3 gland along the milkline

(MGI Ref ID J:60708)

• increased nipple number
  • connected to distinct underlying ductal systems; not connected to the major ductal system of the normal gland

(MGI Ref ID J:60708)

• easily observed at 21 days of age

(MGI Ref ID J:60708)

• most commonly observed laterally to a #4 gland and displaced away from the mid-line

(MGI Ref ID J:60708)

• this phenotype or supernumerary mammary glands comprise 31% of mice observed

(MGI Ref ID J:60708)

integument phenotype

• abnormal mammary gland development
  • Background Sensitivity – 95% of female A/J mice display an altered pattern of mammary gland development compared with C57BL/6 which showed no abnormalities in this study

(MGI Ref ID J:60708)

• abnormal mammary gland pattern
  • 95% of females have abnormal mammary gland development

(MGI Ref ID J:60708)

• abnormal nipple development

(MGI Ref ID J:60708)

• absent mammary gland
  • 55% of females observed have this phenotype

(MGI Ref ID J:60708)

• Background Sensitivity – when observed involves only glands of pair #3

(MGI Ref ID J:60708)

• ectopic mammary gland
  • 29% of females observed had this phenotype

(MGI Ref ID J:60708)

• misplacement is usually observed with gland #3

(MGI Ref ID J:60708)

• ectopic nipples

(MGI Ref ID J:60708)

• increased mammary gland number
  • 31% of the females observed have this phenotype or supernumerary nipples

(MGI Ref ID J:60708)

• occasionally found between glands #2 and #4 or below #3 gland along the milkline

(MGI Ref ID J:60708)

• increased nipple number
  • connected to distinct underlying ductal systems; not connected to the major ductal system of the normal gland

(MGI Ref ID J:60708)

• easily observed at 21 days of age

(MGI Ref ID J:60708)

• most commonly observed laterally to a #4 gland and displaced away from the mid-line

(MGI Ref ID J:60708)

• this phenotype or supernumerary mammary glands comprise 31% of mice observed

(MGI Ref ID J:60708)

Research Applications

This mouse can be used to support research in many areas including:

Mouse/Human Gene Homologs
Muscular dystrophy, limb-girdle
Type 2B

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Genes regulating susceptibility to infectious disease and endotoxin
Immunodeficiency
Specific complement deficiency
Macrophage defects

Research Tools
Immunology, Inflammation and Autoimmunity Research
Specific complement deficiency, C5 complement

Neurobiology Research
Muscular Dystrophy
Limb-Girdle type
Hearing Defects
Age related hearing loss

Sensorineural Research
Hearing Defects
Age related hearing loss
Internal/Organ Research
Lung Defects
COPD
Emphysema

Cardiovascular Research
Diet-Induced Atherosclerosis
Relatively Resistant

Developmental Biology Research
Craniofacial and Palate Defects
congenital cleft palate
Internal/Organ Defects
gonads

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