|
General Comment |
When any organism is stressed by an increase in temperature, a set of protective proteins are synthesized that presumably
function to maintain intracellular homeostasis. Transcription of heat-shock genes (e.g., OMIM 140550) is rapidly induced after
temperature stress. This response is mediated by a promoter element, the heat-shock element (HSE). HSE binds a
multimeric transcriptional stimulatory protein, termed heat-shock factor (HSF).
Heat shock transcription factors activate heat-shock response genes under conditions of heat or other stresses. Using the partial peptide sequence of HSF1 from HeLa cells to screen a human T-cell cDNA library . HSF1 and HSF2 encode proteins that bind specifically to
the heat-shock element and have homology to HSFs of other species.
NCBI Summary:
HSF2, as well as the related gene HSF1, encodes a protein that binds specifically to the heat-shock element and has homology to HSFs of other species. Heat shock transcription factors activate heat-shock response genes under conditions of heat or other stresses. Although the names HSF1 and HSF2 were chosen for historical reasons, these peptides should be referred to as heat-shock transcription factors.
|
|
Mutations |
1 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: subfertile
Comment: Kallio M, et al 2002 reported brain abnormalities, defective meiotic chromosome synapsis and
female subfertility in HSF2 null mice.
Heat shock factor 2, one of the four vertebrate HSFs, transcriptional regulators of heat
shock gene expression, is active during embryogenesis and spermatogenesis, with
unknown functions and targets. By disrupting the Hsf2 gene, the authors show that, although
the lack of HSF2 is not embryonic lethal, Hsf2(-/-) mice suffer from brain
abnormalities, and meiotic and gametogenesis defects in both genders. The
disturbances in brain are characterized by the enlargement of lateral and third
ventricles and the reduction of hippocampus and striatum, in correlation with HSF2
expression in proliferative cells of the neuroepithelium and in some ependymal cells
in adults.
Hsf2(-/-) females suffer from multiple fertility defects: the production of abnormal
eggs, the reduction in ovarian follicle number and the presence of hemorrhagic cystic
follicles are consistent with meiotic defects. Hsf2(-/-) females also display hormone
response defects, that can be rescued by superovulation treatment, and exhibit
abnormal rates of luteinizing hormone receptor mRNAs.
Hsf2-/- females were found to have
dramatic ovulation problems. Only three Hsf2-/- females produced eggs, resulting in a total average of 3.5 eggs per Hsf2-/-
female. Seven out of 10 Hsf2+/+ females ovulated with a total average of 7.4 eggs per female. The average number of
fertilized eggs was 0.6 fertilized egg per Hsf2-/- female versus 4.9 per Hsf2+/+ female (P < 0.05). Indeed, Hsf2-/- females
frequently produced abnormal eggs: 43.7% of the eggs were fragmented or without polar bodies (versus 5.4% for control
females) or were unfertilized (40.6% with only one polar body versus 28.4% in controls).
The authors attempted to rescue ovulation in Hsf2-/- females by administration
of pregnant mare serum gonadotropin (PMSG/FSH)/human chorionic gonadotropin (hCG/LH) to 21- to 27-day-old mice, a
treatment used to induce superovulation. All Hsf2-/- females were able to ovulate after this treatment. A total of 35.1 ? 22.5
eggs were ovulated by Hsf2-/- females (n = 16), statistically comparable (P = 0.853) with 37.2 ? 11.7 eggs in wild-type
females (n = 5). However, while the eggs of wild-type females were able to develop in vitro to the two-cell stage with
good scores (27.3 ? 1.7 eggs; 78.3% of the total ovulated eggs), eggs of Hsf2-/- females were often abnormal and only
10.2 ? 5.8 eggs (29.2% of the total) developed to the two-cell stage, which was significantly lower (P = 0.0132). The fact
that 70% of the eggs ovulated by Hsf2-/- females were abnormal is suggestive of meiotic problems. Since superovulation
treatment rescued ovulation in Hsf2-/- females, part of the ovarian defects observed in pubescent Hsf2-/- females may be
secondary to disturbed hormonal physiological concentrations of gonadotropins or ovarian function alterations.
|