Posted 7 December 2010
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.
Mouse strain: C57BL/6; Background: C57Bl/6.
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).
Ko mice are viable but have lower birth frequency (2).
Contact: Dr. Jada Lewis
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224
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.
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.