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Conference Paper: Generation and characterization of sodium/myo-inositol cotransporter (SMIT) knockout mice

TitleGeneration and characterization of sodium/myo-inositol cotransporter (SMIT) knockout mice
Authors
Issue Date2001
PublisherFederation of American Societies for Experimental Biology
Citation
Experimental Biology 2001, New Orlando, FL, 31 March-4 April 2001. In The FASEB Journal, 2001, v, 15 n. 4, p. A102 How to Cite?
AbstractCells that experience prolonged hypertonic environment undergo various adaptations. One of these changes is the accumulation of small organic osmolytes which do not perturb the behavior of key metabolic enzymes. Myo-inositol is one of these osmolytes. Mammalian cells accumulate myo-inositol through an active transporter, the Sodium/Myo-inositol cotransporter (SMIT), which is also called SLC5A3 for solute carrier family 5, number 3 protein. Previous observations suggest that SMIT may be involved in osmoregulation, renal function, production of phosphatidylinositol and neurological disorders. Although inhibitors against SMIT can be used to understand its function, the in vivo efficacy and specificity of these drugs are not clear. Therefore, we generated SMIT knockout mice to delineate the role of SMIT under both normal and disease conditions. There is no apparent abnormality with the heterozygous SMIT knockout mice. However, breeding between the heterozygous mice (37 litters) generated pups with the following genotypes: 22 homozygous(-/-), 161 heterozygous (+/-) and 90 wildtype (+/+). This indicates that only 25% of (-/-) survived into adulthood. In order to determine whether the mice die in utero or after birth, we sacrificed 8 pregnant heterozygous females, which were mated with heterozygous males, at embryonic day 18.5 (E18.5). The average litter size was 9.4 and the genotypic ratio followed mandellian ratio (16 -/- : 41 +/- : 18 +/+). This indicates all homozygous SMIT knockout can survive up to E18.5 but lethality occurred after birth. Northern blot hybridization showed that the 12kb transcript of SMIT mRNA is absent in the survival adult SMIT knockout mice. HPLC analysis showed that there was approximately 70% reduction in tissue myo-inositol and changes in osmolytes profile was also observed in the brain and kidney of homozygous knockout mice. However, no significant difference was observed in the volume of 24 hr water intake and urination.
Persistent Identifierhttp://hdl.handle.net/10722/108791
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775

 

DC FieldValueLanguage
dc.contributor.authorLee, MKen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorChung, SKen_HK
dc.date.accessioned2010-09-26T00:54:36Z-
dc.date.available2010-09-26T00:54:36Z-
dc.date.issued2001en_HK
dc.identifier.citationExperimental Biology 2001, New Orlando, FL, 31 March-4 April 2001. In The FASEB Journal, 2001, v, 15 n. 4, p. A102-
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/108791-
dc.description.abstractCells that experience prolonged hypertonic environment undergo various adaptations. One of these changes is the accumulation of small organic osmolytes which do not perturb the behavior of key metabolic enzymes. Myo-inositol is one of these osmolytes. Mammalian cells accumulate myo-inositol through an active transporter, the Sodium/Myo-inositol cotransporter (SMIT), which is also called SLC5A3 for solute carrier family 5, number 3 protein. Previous observations suggest that SMIT may be involved in osmoregulation, renal function, production of phosphatidylinositol and neurological disorders. Although inhibitors against SMIT can be used to understand its function, the in vivo efficacy and specificity of these drugs are not clear. Therefore, we generated SMIT knockout mice to delineate the role of SMIT under both normal and disease conditions. There is no apparent abnormality with the heterozygous SMIT knockout mice. However, breeding between the heterozygous mice (37 litters) generated pups with the following genotypes: 22 homozygous(-/-), 161 heterozygous (+/-) and 90 wildtype (+/+). This indicates that only 25% of (-/-) survived into adulthood. In order to determine whether the mice die in utero or after birth, we sacrificed 8 pregnant heterozygous females, which were mated with heterozygous males, at embryonic day 18.5 (E18.5). The average litter size was 9.4 and the genotypic ratio followed mandellian ratio (16 -/- : 41 +/- : 18 +/+). This indicates all homozygous SMIT knockout can survive up to E18.5 but lethality occurred after birth. Northern blot hybridization showed that the 12kb transcript of SMIT mRNA is absent in the survival adult SMIT knockout mice. HPLC analysis showed that there was approximately 70% reduction in tissue myo-inositol and changes in osmolytes profile was also observed in the brain and kidney of homozygous knockout mice. However, no significant difference was observed in the volume of 24 hr water intake and urination.-
dc.languageengen_HK
dc.publisherFederation of American Societies for Experimental Biology-
dc.relation.ispartofThe FASEB Journalen_HK
dc.titleGeneration and characterization of sodium/myo-inositol cotransporter (SMIT) knockout miceen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.hkuros61093en_HK

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