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DBA2J

DBA2J

DBA/2J possesses various mutations contributing to its pathologies in audition and vision.

For audition, there are Cdh23ahl, asp2 mutation and also 3 more recessive alleles, together they induce various auditory pathologies, ranging from high-frequency hearing loss to cochlear pathologies, from neurodegeneration to audiogenic seizures.

For vision, there are Tyrplisa and GpnmbR150X alleles, together they induce various visual pathologies, especially in iris and IOP, that closely resemble human hereditary glaucoma.

Moreover, DBA/2J also exhibit characteristic susceptibility to various pathological states, such as atherosclerotic aortic lesions and calcareous pericarditis, and to various chemical substances, ranging from alcohol to morphine, from haloperidol to phytohemagglutinin.

All these characteristic make DBA/2J a versatile animal model for various research field, ranging from neurobiology to sensorineural research.

Add Animal Model Information


Genetics

  • DBA/2J mutations and genes contributing to its auditory and visual pathologies and chemical susceptibility:
  • Audition: 
  • Homozygous for the age related hearing loss 1 mutation, Cdh23ah1.(The Jackson Laboratory)
  • Possessing the asp2 mutation, which induce the audiogenic seizures in young mutant.(The Jackson Laboratory)
  • Possess 3 recessive alleles which can induce progressive cochlear pathology(The Jackson Laboratory)
  • Vision: Possess two alleles, Tyrplisa and GpnmbR150X, which contribute to the eye phenotype(The Jackson Laboratory)
  • DBA/2J also have a ~2.4kb deletion in the 3’ end of the Klrd1 gene, which encodes for CD94, and thereby prevents translation (although not transcription) and its subsequent cell surface expression.(The Jackson Laboratory)
  • The lack of cell surface expression of CD94 might in turn lead to the lack of cell surface expression of CD94/NKG2A receptors, which are typically on the surface of the majority of fetal NK cells and might contribute to self tolerance and enable NK cells to differentiate the MHC Ihigh and MHC Ilow target cells.(The Jackson Laboratory)

Auditory Pathology

  • Homozygous for the age related hearing loss 1 mutation, Cdh23ahl, DBA/2J exhibit progressive hearing loss, which is already serious by 3 months.(The Jackson Laboratory)
  • They also experience high-frequency hearing loss starting between 3 to 4 weeks and progressively aggravating by 2 to 3 months.(The Jackson Laboratory)
  • They also have 3 recessive alleles, which can induce progressive cochlear pathology starting from the organ of Corti.(The Jackson Laboratory)
  • The cochlear pathologies, ranging from neurodegeneration to decrement in anteroventral cochlear nucleus volume, are parallel to the progressive peripheral hearing loss, and therefore might be inter-related.(The Jackson Laboratory)
  • Possessing the asp2 mutation, young DBA/2J mice also exhibit susceptibility to audiogenic seizures, which however subside when they reach adulthood.(The Jackson Laboratory)

Visual Pathology

  • Tow alleles of DBA/2J, Tyrplisa and GpnmbR150X, contribute to its eye phenotype, which include the progressive eye abnormalities, ranging from iris atrophy to anterior synechia, from iris pigment dispersion to elevated intraocularpressure (IOP). The pathologies onset between 3 and 4 months and tightly mimick human hereditary glaucoma.(The Jackson Laboratory)
  • Female-biased sexual dimorphism exist in various visual pathologies.(The Jackson Laboratory)
  • For instance, signs of transillumination of peripheral iris and iris pigment epithelium loss are observable in up to 56% of females but merely 15% of males(The Jackson Laboratory)
  • increment in IOP is also exhibited in some females as early as 6 months(The Jackson Laboratory)
  • although both males and females exhibit increment in IOP by 9 months, the pressures in females (mean: 20.3 +/-79; 1.8 mmHg) are still higher than that in males(mean: 16.2 +/-79; 1.4mmHg).(The Jackson Laboratory)
  • Moreover, significant widespread transillumination and thickening of the iris border are exhibited in all mice by 6 to 7 months(The Jackson Laboratory)
  • Degenerations of retinal ganglion cell, cholinergic and GABAergic amacrine cell are also evident via retinal histopathology(The Jackson Laboratory)

Pathological Susceptibility

Low susceptibility to:

High susceptibility to:

Chemical Susceptibility

High sensitivity to:

Low sensitivity to:

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