Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion
Barth syndrome (BTHS) is caused by mutations in tafazzin resulting in deficits in cardiolipin remodeling that alter major metabolic processes. The tafazzin gene is encoded on the X chromosome, and therefore BTHS primarily affects males. Female carriers are typically considered asymptomatic, but age-...
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MDPI AG
2023-09-01
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| author | Michelle V. Tomczewski John Z. Chan Duaa M. Al-Majmaie Ming Rong Liu Alex D. Cocco Ken D. Stark Douglas Strathdee Robin E. Duncan |
| author_facet | Michelle V. Tomczewski John Z. Chan Duaa M. Al-Majmaie Ming Rong Liu Alex D. Cocco Ken D. Stark Douglas Strathdee Robin E. Duncan |
| author_sort | Michelle V. Tomczewski |
| collection | DOAJ |
| description | Barth syndrome (BTHS) is caused by mutations in tafazzin resulting in deficits in cardiolipin remodeling that alter major metabolic processes. The tafazzin gene is encoded on the X chromosome, and therefore BTHS primarily affects males. Female carriers are typically considered asymptomatic, but age-related changes have been reported in female carriers of other X-linked disorders. Therefore, we examined the phenotype of female mice heterozygous for deletion of the tafazzin gene (<i>Taz</i>-HET) at 3 and 12 months of age. Food intakes, body masses, lean tissue and adipose depot weights, daily activity levels, metabolic measures, and exercise capacity were assessed. Age-related changes in mice resulted in small but significant genotype-specific differences in <i>Taz</i>-HET mice compared with their female <i>Wt</i> littermates. By 12 months, <i>Taz</i>-HET mice weighed less than <i>Wt</i> controls and had smaller gonadal, retroperitoneal, and brown adipose depots and liver and brain masses, despite similar food consumption. Daily movement, respiratory exchange ratio, and total energy expenditure did not vary significantly between the age-matched genotypes. <i>Taz</i>-HET mice displayed improved glucose tolerance and insulin sensitivity at 12 months compared with their <i>Wt</i> littermates but had evidence of slightly reduced exercise capacity. Tafazzin mRNA levels were significantly reduced in the cardiac muscle of 12-month-old <i>Taz</i>-HET mice, which was associated with minor but significant alterations in the heart cardiolipin profile. This work is the first to report the characterization of a model of female carriers of heterozygous tafazzin deficiency and suggests that additional study, particularly with advancing age, is warranted. |
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| last_indexed | 2024-03-10T23:01:39Z |
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| spelling | doaj.art-a6816bbca01e4a64aa89ac936befd0202023-11-19T09:38:57ZengMDPI AGBiology2079-77372023-09-01129123810.3390/biology12091238Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin DeletionMichelle V. Tomczewski0John Z. Chan1Duaa M. Al-Majmaie2Ming Rong Liu3Alex D. Cocco4Ken D. Stark5Douglas Strathdee6Robin E. Duncan7Department of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, 200 University Ave W., BMH1044, Waterloo, ON N2L 3G1, CanadaDepartment of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, 200 University Ave W., BMH1044, Waterloo, ON N2L 3G1, CanadaDepartment of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, 200 University Ave W., BMH1044, Waterloo, ON N2L 3G1, CanadaDepartment of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, 200 University Ave W., BMH1044, Waterloo, ON N2L 3G1, CanadaDepartment of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, 200 University Ave W., BMH1044, Waterloo, ON N2L 3G1, CanadaDepartment of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, 200 University Ave W., BMH1044, Waterloo, ON N2L 3G1, CanadaTransgenic Technology Laboratory, Cancer Research UK Beatson Institute, Switchback Road, Glasgow G61 1BD, Scotland, UKDepartment of Kinesiology and Health Sciences, Faculty of Health, University of Waterloo, 200 University Ave W., BMH1044, Waterloo, ON N2L 3G1, CanadaBarth syndrome (BTHS) is caused by mutations in tafazzin resulting in deficits in cardiolipin remodeling that alter major metabolic processes. The tafazzin gene is encoded on the X chromosome, and therefore BTHS primarily affects males. Female carriers are typically considered asymptomatic, but age-related changes have been reported in female carriers of other X-linked disorders. Therefore, we examined the phenotype of female mice heterozygous for deletion of the tafazzin gene (<i>Taz</i>-HET) at 3 and 12 months of age. Food intakes, body masses, lean tissue and adipose depot weights, daily activity levels, metabolic measures, and exercise capacity were assessed. Age-related changes in mice resulted in small but significant genotype-specific differences in <i>Taz</i>-HET mice compared with their female <i>Wt</i> littermates. By 12 months, <i>Taz</i>-HET mice weighed less than <i>Wt</i> controls and had smaller gonadal, retroperitoneal, and brown adipose depots and liver and brain masses, despite similar food consumption. Daily movement, respiratory exchange ratio, and total energy expenditure did not vary significantly between the age-matched genotypes. <i>Taz</i>-HET mice displayed improved glucose tolerance and insulin sensitivity at 12 months compared with their <i>Wt</i> littermates but had evidence of slightly reduced exercise capacity. Tafazzin mRNA levels were significantly reduced in the cardiac muscle of 12-month-old <i>Taz</i>-HET mice, which was associated with minor but significant alterations in the heart cardiolipin profile. This work is the first to report the characterization of a model of female carriers of heterozygous tafazzin deficiency and suggests that additional study, particularly with advancing age, is warranted.https://www.mdpi.com/2079-7737/12/9/1238tafazzincardiolipinBarth syndromemitochondriaenergy metabolismexercise capacity |
| spellingShingle | Michelle V. Tomczewski John Z. Chan Duaa M. Al-Majmaie Ming Rong Liu Alex D. Cocco Ken D. Stark Douglas Strathdee Robin E. Duncan Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion Biology tafazzin cardiolipin Barth syndrome mitochondria energy metabolism exercise capacity |
| title | Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion |
| title_full | Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion |
| title_fullStr | Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion |
| title_full_unstemmed | Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion |
| title_short | Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion |
| title_sort | phenotypic characterization of female carrier mice heterozygous for tafazzin deletion |
| topic | tafazzin cardiolipin Barth syndrome mitochondria energy metabolism exercise capacity |
| url | https://www.mdpi.com/2079-7737/12/9/1238 |
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