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TL;DR
This study created a liver-specific knockout mouse model for thymidine kinase 2 (Tk2) deficiency and found that, unlike the fatal whole-body knockout, these mice survived normally but developed abnormal liver fat accumulation.
PLOS ONE · 9 authors, 4 centres
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This study created a liver-specific knockout mouse model for thymidine kinase 2 (Tk2) deficiency and found that, unlike the fatal whole-body knockout, these mice survived normally but developed abnormal liver fat accumulation.
The study generated a liver-specific Tk2 knockout mouse model to investigate the consequences of mtDNA depletion confined to the liver. In contrast to total Tk2 knockout mice, which die around two weeks of age, liver-specific knockout mice survived to at least 1.5 years of age despite maintaining liver mtDNA levels at approximately 30% (male) and 40% (female) of wild-type. The primary phenotypic abnormality was a significantly increased relative liver weight in male mice, with a similar trend in females, and histological evidence of increased hepatic lipid accumulation. Electron microscopy showed normal mitochondrial morphology. The authors suggest that other deoxyribonucleoside kinases, likely deoxycytidine kinase, may partially compensate for TK2 deficiency to maintain a low but stable mtDNA level sufficient for survival and basic mitochondrial function, but not for normal lipid metabolism.