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An Allelic/Nonallelic Series of BMP-Deficient Limbs

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posted on 21.02.2013, 13:01 by Amitabha Bandyopadhyay, Kunikazu Tsuji, Karen Cox, Brian D Harfe, Vicki Rosen, Clifford J Tabin

(A–D) Prx1::cre efficiently recombines Bmp2 and Bmp4 conditional alleles in the limbs. Bmp2 (A and B) and Bmp4 (C and D) whole mount mRNA in situ hybridization in the limb. Wild-type (A) and Bmp2C/C; Prx1::cre (B) are forelimbs from E10.5 mouse embryos. Mesenchymal expression [asterisk (A)] of Bmp2 is abolished in Bmp2C/C; Prx1::cre embryo while the AER expression [black arrow (A and B)] of Bmp2 persists. Note that pink staining in the central region of the limb bud in (B) is nonspecific background. Wild-type (C) and Bmp4C/C; Prx1::cre (D) are forelimbs from E10.5 mouse embryos. Mesenchymal expression [red arrow (C)] of Bmp4 is abolished in Bmp4C/C; Prx1::cre embryo while the AER expression [black arrow (C and D)] of Bmp4 persists.

(E–T) Depletion of BMP2 and BMP4 together causes severe limb skeletal defects. (E–T) Whole mount skeletons from newborn animals stained with Alcian blue and Alizarin red. (E–L) Forelimbs, (M–T) hindlimbs. (E and M) Wild-type, (F and N) Bmp2C/C; Prx1::cre, (G and O) Bmp4C/C; Prx1::cre, (H and P) Bmp7/, (I and Q) Bmp2C/C; Bmp4+/C; Prx1::cre, (J and R) Bmp2+/C; Bmp4C/C; Prx1::cre, (K and S) Bmp2C/C; Bmp4C/C; Prx1::cre, (L and T) Bmp2C/C, Bmp7/; Prx1::cre. Thin red arrow in (F), (I), and (L), defective scapula; thick red arrow in (T), failure of fibula to articulate with knee, and thick black arrow in (L) and (T), missing phalanx in digit III.

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