Platelet-derived growth factor receptor-beta constitutive activity promotes angiogenesis in vivo and in vitro.

Objective: Knockout studies have demonstrated crucial roles for the platelet-derived growth factor-B and its cognate receptor, platelet-derived growth factor receptor-beta (PDGFR-beta), in blood vessel maturation, that is, the coverage of newly formed vessels with mural cells/pericytes. This study describes the consequences of a constitutively activating mutation of the PDGFR-beta (Pdgfrb(D849V)) introduced into embryonic stem cells with respect to vasculogenesis/angiogenesis in vitro and in vivo.

Methods And Results: Embryonic stem cells were induced to either form teratomas in vivo or embryoid bodies, an in vitro model for mouse embryogenesis.

An activating mutation in the PDGF receptor-beta causes abnormal morphology in the mouse placenta.

An oncogenic D842V mutation in the platelet-derived growth factor (PDGF) alpha-receptor (Pdgfra) has recently been described in patients with gastrointestinal stromal tumors. In order to test if the same mutation would confer oncogenic properties to the homologous PDGF beta-receptor (Pdgfrb), the corresponding aspartic acid residue at position 849 of Pdgfrb was changed into valine (D849V) using a knock-in strategy. This mutation turned out to be dominantly lethal and caused death even in chimeras (from 345 transferred chimeric blastocysts, no living coat chimeras were detected).

A novel Krüppel-Associated Box identified in a panel of mammalian zinc finger proteins.

Krüppel-related zinc finger proteins probably constitute the largest individual family of transcription factors in mammals. These proteins often carry a potent repressor domain called the Krüppel Associated Box (KRAB), which is known to effectively repress transcription through interaction with transcriptional intermediary factor 1beta (TIF1beta). Here we report the isolation and characterization of a novel human KRAB A zinc finger protein, HZF12.

MZF6D, a novel KRAB zinc-finger gene expressed exclusively in meiotic male germ cells.

Spermatogenesis takes place in the seminiferous tubule in the testes and culminates in the production of spermatozoa (male gametes). Here we report the identification of a novel mouse zinc-finger gene, MZF6D, which is selectively expressed in meiotic spermatocytes. The MZF6D protein contains an N-terminally located repressor domain, a KRAB domain, followed by at least seven successive Krüppel zinc-finger motifs.

KRAB zinc finger proteins: an analysis of the molecular mechanisms governing their increase in numbers and complexity during evolution.

Krüppel-related zinc finger proteins, with 564 members in the human genome, probably constitute the largest individual family of transcription factors in mammals. Approximately 30% of these proteins carry a potent repressor domain called the Krüppel associated box (KRAB). Depending on the structure of the KRAB domain, these proteins have been further divided into three subfamilies (A + B, A + b, and A only).