Reproductive and neurological Quaking(viable) phenotypes in a severe combined immune deficient mouse background.
ABSTRACT The quaking(viable) (qkv) mutation, a spontaneous deletion of a multigenic region encompassing roughly 1 Mb at 5.9 cM on the proximal end of mouse chromosome 17, causes severe trembling in all homozygous animals and infertility in all homozygous males. Physiologically, quaking mice exhibit dysmyelination and postmeiotic spermatogenic arrest. Molecular defects in Qkv mice occur in the affected tissues, indicating the primary causes of these pathologies are cell autonomous. However, because both the reproductive and neurological defects are in immune-privileged sites and because some similar pathologies at both sites have been shown to be immune mediated, we tested whether the immune system participates secondarily in manifestation of Qkv phenotypes. The qkv mutation was bred into a severe combined immune-deficient mouse line (SCID; devoid of mature B and T cells) and penetrance of the neurological and the male sterile phenotypes was measured. Results showed that neither defect was ameliorated in the immune-deficient background. We conclude that the Qkv pathologies do not likely involve a B- or T-cell-dependent response against these immune-privileged sites.
Article: The quaking gene product necessary in embryogenesis and myelination combines features of RNA binding and signal transduction proteins.[show abstract] [hide abstract]
ABSTRACT: The mouse quaking gene, essential for nervous system myelination and survival of the early embryo has been positionally cloned. Its sequence implies that the locus encodes a multifunctional gene used in a specific set of developing tissues to unite signal transduction with some aspect of RNA metabolism. The quaking(viable) (qkv) mutation has one class of messages truncated by a deletion. An independent ENU-induced mutation has a nonconservative amino acid change in one of two newly identified domains that are conserved from the C. elegans gld-1 tumour suppressor gene to the human Src-associated protein Sam68. The size and conservation of the quaking gene family implies that the pathway defined by this mutation may have broad relevance for rapid conveyance of extracellular information directly to primary gene transcripts.Nature Genetics 04/1996; 12(3):260-5. · 35.53 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: A number of recessive autosomal genes cause male infertility. Male mice homozygous for the blind-sterile (bs/bs) and quaking-sterile (qk/qk) gene mutations are sterile, because they either do not produce any spermatozoa or produce only a few abnormal spermatozoa. Mice lacking the cyclic AMP responsive-element modulator gene are sterile due to failure of spermiogenesis. All these mice, however, are able to produce fertile offspring when their spermatozoa or round spermatids are injected into oocytes of normal females. This implies that genetic and epigenetic elements necessary for syngamy and embryonic development are established in round spermatids and spermatozoa of these animals, even though their spermatogenic cells are destined to die (bs/bs and qk/qk) or are programmed to undergo apoptosis (cyclic AMP responsive-element modulator-null) without becoming functional spermatozoa.Proceedings of the National Academy of Sciences 03/2004; 101(6):1691-5. · 9.68 Impact Factor