Posted 7 December 2010

General Information

Transgene: Replaced an internal 4.7 kb EcoRV–EcoRI fragment, encoding exons 2–13 of the PGRN gene, with a neo-cassette and ligated the diphtheria toxin A (DT-A) fragment to the 5’end of the vector. The neomycin resistance gene, under the control of the phosphoglycerate kinase (PGK) 1 promoter, was inserted as a positive selection marker and DT-A fragment DNA, under the polyoma enhancer/herpes simplex virus thymidine promoter (MC-1), was used as a negative selection mechanism for the screening of recombinant embryonic stem (ES) cells. The targeting vector, linearized by ApaI, was electroporated into E14.1 ES cells. ES cells were aggregated with two (C57BL/6×DBF1) embryos F1 eight cell stage embryos.

Mutation: N/A

Promoter: N/A

Mouse strain: C57BL/6; Background: C57Bl/6.

Phenotype

Neuropathological Analysis:

Ko mice developed age-associated, abnormal intraneuronal ubiquitin-positive autofluorescent lipofuscin. They also developed microgliosis, astrogliosis, and tissue vacuolation, with focal neuronal loss and severe gliosis apparent in the oldest GRN-/- mice (2).

Behavioral Phenotype:

Ko mice are viable but have lower birth frequency (2).

Availability

Contact: Dr. Jada Lewis
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224

References

Primary:

Kayasuga Y, Chiba S, Suzuki M, Kikusui T, Matsuwaki T, Yamanouchi K, Kotaki H, Horai R, Iwakura Y, Nishihara M. Alteration of behavioural phenotype in mice by targeted disruption of the progranulin gene. Behav Brain Res 2007, 185:110–118. Abstract

Associated:

Ahmed Z, Sheng H, Xu YF, Lin WL, Innes AE, Gass J, Yu X, Hou H, Chiba S, Yamanouchi K, Leissring M, Petrucelli L, Nishihara M, Hutton ML, McGowan E, Dickson DW, Lewis J. Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful aging. Am J Pathol. 2010 Jul;177(1):311-24. Abstract