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, we show that, although the lack of HSF2 is not embryonic lethal, Hsf2(-/-) mice suffer from brain abnormalities, and meiotic and gameto genesis 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. Many developing spermatocytes are eliminated via apoptosis in a stage-specific manner in Hsf2(-/-) males, and pachytene spermatocytes also display structural defects in the synaptonemal complexes between homologous chromosomes. 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.
Kallio
Marko
M
Turku Centre for Biotechnology, University of Turku, Abo Akademi University, FIN-20520 Turku, Finland.
Chang
Yunhua
Y
Manuel
Martine
M
Alastalo
Tero-Pekka
TP
Rallu
Murielle
M
Gitton
Yorick
Y
Pirkkala
Lila
L
Loones
Marie-Thérèse
MT
Paslaru
Liliana
L
Larney
Severine
S
Hiard
Sophie
S
Morange
Michel
M
Sistonen
Lea
L
Mezger
Valérie
V
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism*; D002875:Chromosomes / Q000648:ultrastructure*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000235:genetics; D005822:Genetic Vectors; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006579:Heterozygote; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000235:genetics*; D007763:Lac Operon; D008297:Male; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D010053:Ovary / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013737:Testis / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
D006360:Heat-Shock Proteins; D014157:Transcription Factors; C070389:HSF2 protein, human; D001616:beta-Galactosidase