Characterization of Mammary Gland Development in CEBPb2 Transgenic Mice

1
Characterization of Mammary Gland Development in
C/EBPb-2 Transgenic Mice
Linda M. Bundy 1, Erin M. Eaton 1, Rebecca Cook
2, Rachel Jerrell 1, Linda Sealy 1.
1 Department of Molecular Physiology
Biophysics, 2 Department of Cancer Biology,
Vanderbilt University Medical School, Nashville,
TN, 37232.
C/EBP Beta Basics
Experimental Observations
Ectopic Overexpression of tagged C/EBPb-2 in
PMECs Promotes Hyperplastic Growth
Upregulation of COX-2 Observed in C/EBPb-2
Transgenic Mammary Glands
Primary mammary epithelial cells (PMECs) were
harvested from mature wt virgin FVB/N females,
placed in culture and infected with either
LZRS-GFP only (panel A) LZRS-His-C/EBPb2-IRES-GFP
(panel B) or LZRS-His-C/EBPb1-IRES-GFP (panel
C) virus. Two weeks later, the infected PMECs
were implanted into the cleared fatpads of 3-4
week old recipient FVB/N females. Wholemounts of
the modified fatpads were prepared 6 weeks after
implantation.
40 X magnification
COX-2 overexpression detected via IHC in the
virgin mammary glands of non- transgenic (panels
AB) and MMTV-C/EBPbeta-2 transgenic females
(panels C D). Animals in panels A, C D are
age-matched littermates.
Abnormal Mammary Histology is Accelerated in
Multiparous Transgenic Females
A
B
C
5 X HE
10 X HE
40 X HE
Typical mammary gland architecture of a 1 year
old multiparous (4 litters) C/EBPbeta-2
Transgenic shown in panels A-C. Note the
extensive keratin and collagen deposits as well
as the numerous mitotic figures.
D
4 X Magnification
E
F
20 X magnification
40 X Magnification
Typical mammary gland architecture observed in
20-24 month old virgin C/EBPbeta-2 Transgenics
shown in panels D-F. Although similar to that
observed in the younger multiparous animals
(panels A-C), the epithelial growth of virgin
animals is not as extensive as that of younger
mulitparous C/EBPbeta-2 transgenics.