By Nanna M. Andersen | Published: 17.04.22 | Edited: 21.07.23 | Dansk oversættelse: 21.07.23 There are many Dwarf genes found in the rat gene pool, but only one is found in the fancy rat community, known as the Spontaneous Dwarf Rat or SDR. The gene affected in SDR is GH1, which is represented by the gene symbol dr. This mutation originated in laboratories from Sprague-Dawley rats in 1977. SDR rats possess a mutation in the growth hormone gene that results in the Dwarf body type. Interestingly, this same gene also inhibits cancer growth throughout the rat's life. Studies on SDR rats' longevity have revealed that males live approximately 2.4 years (29.3 months, +/- 3.3), while females live approximately 2.2 years (26.8 months, +/- 5.3). This indicates that the life expectancy of SDR rats is not similar to that of standard rats. In fact, SDR rats derived from the Sprague-Dawley strain show an increased life expectancy of 20-40% for males and 10-20% for females. SDR rats also exhibit a decrease in pituitary and mammary tumors, as well as in severe chronic nephropathy (kidney function deterioration). Ghrelin, also known as the hunger hormone, is more than double in SDR rats compared to standard rats. This may explain why some Dwarf rats struggle to maintain a healthy weight, as increased ghrelin levels induce weight gain by reducing fat utilization. The most common ailments observed in naturally deceased SDR rats include myocardial fibrosis (scar tissue in the heart), atrial thrombosis (blood clot), malocclusion, cerebral hemorrhage (stroke), and chronic nephropathy (kidney damage). These results match that of standard rats. It is unclear what mechanisms causes the longevity of Dwarf rats considering they live longer than standard rats from the same line. It is challenging to directly compare these results with the Dwarfs in the fancy rat community due to selective breeding employed by reputable breeders. However, these findings provide a detailed picture of ailments that rats may suffer from in old age, regardless of being Dwarf or standard. Another study demonstrated that SDR rats live on average 38% longer than Sprague-Dawley rats. This increased lifespan is supported by a decrease in 8-oxodG content, a marker for oxidative DNA damage, indicating reduced oxidative stress in the liver, kidney, and lung of SDR rats. Furthermore, SDR rats exhibit higher resistance to oxygen levels, suggesting that enhanced hydrogen peroxide elimination contributes to their improved resistance to oxidative stress and potential lifespan extension. As mentioned earlier, Dwarf rats have elevated levels of ghrelin, the hunger hormone, which may contribute to obesity. This could be attributed to the fact that Dwarf rats have a lower energy metabolic rate compared to standard rats. Consequently, adipose tissue (body fat) may accumulate in SDR rats due to significantly lower energy expenditure relative to energy intake. Interestingly, despite having more body fat, SDR rats experience an increase in visceral fat (fat around the internal organs) as they age, similar to standard rats. Body fat and visceral fat are not the same type of fat. Visceral fat is considered the more dangerous one as it surrounds the internal organs in the abdominal cavity, liver, pancreas and kidneys. However, the excess body fat does not negatively affect their longevity. Despite being mostly cancer-free and having an extended lifespan, SDR rats exhibit a small decrease in spatial learning and memory. In a Y-maze Test, where the rat is placed in one of three arms of the maze (each arm measuring 40 cm), SDR rats are less likely to alter their route and explore all arms. This suggests impaired spatial learning and memory compared to standard rats, although the exact mechanisms are still unclear. References
Dwarf Rotter
Der er mange forskellige Dwarf gener, men der findes kun ét Dwarf genet i Fancyen og dette kaldes Spontaneous Dwarf Rat eller SDR. Det påvirkede gen ansvarlig for SDR er GH1, som er repræsenteret af gen-symbolet "dr". Denne mutation opstod i laboratorier med Sprague-Dawley rotter i 1977. SDR-rotter har en mutation i væksthormon-genet, der resulterer i Dwarf kropsformen. Interessant nok hæmmer det samme gen også kræftvækst. Undersøgelser af Sprague-Dawley SDR-rotters levetid har vist, at hanner lever cirka 2,4 år (29,3 måneder, +/- 3,3), mens hunner lever cirka 2,2 år (26,8 måneder, +/- 5,3). Dette indikerer, at forventet levetid for Sprague-Dawley SDR-rotter er længere end normalt størrelse rotter fra samme linje. Faktisk viser SDR-rotter afledt af Sprague-Dawley-stammen en forøget levetid på 20-40% for hanner og 10-20% for hunner. SDR-rotter viser også et fald i hypofyse- og mælkekirteltumorer samt alvorlig kronisk diabetisk nyresydom (giver nedsat nyrefunktionen). Ghrelin, også kendt som sult-hormonet, er mere end dobbelt så højt i Sprague-Dawley SDR-rotter sammenlignet med standard rotter. Dette kan forklare, hvorfor nogle dværg-rotter har svært ved at opretholde en sund vægt, da øgede ghrelin-niveauer fører til vægtøgning ved at reducere fedtudnyttelsen i kroppen. De mest almindelige lidelser, der observeres hos naturligt afdøde SDR-rotter, inkluderer arvæv i hjertet, blodprop, tandstillingsfejl, slagtilfælde og nyreskade. Disse er identisk med resultater fra standard rotter. Det tyder dog på at Dwarf rotter udvikler disse sygdomme senere i livet eller sygdommen udvikler sig langsommere på grund af Dwarf genet. Det er svært at sige præcis, hvilken mekanisme gør at Dwarf rotter levede længere end standard rotterne i samme linje. Det er udfordrende at direkte sammenligne disse resultater med Dwarf i det Fancyen på grund af den selektive avl, som anvendes af kyndige opdrættere, og grundet undersøgelsens rotter. Resultaterne heri giver dog et detaljeret billede af sygdomme, som rotter kan lide af i en alderdom, uanset om de er Dwarf eller standard. En anden undersøgelse viste, at deres SDR-rotter i gennemsnit lever 38% længere end Sprague-Dawley rotter. Denne forlængede levetid understøttes af et fald i 8-oxodG-indhold, en markør for oxidativ DNA-skade, hvilket tyder på reduceret oxidativ stress i leveren, nyrerne og lungerne hos deres SDR-rotter. Derudover viser deres SDR-rotter en øget modstand mod ændringer i ilt-niveauer, hvilket antyder, at en forbedret brintoverilte-eliminering bidrager til deres forbedrede modstand mod oxidativ stress og mulig forlænget levetid. Som tidligere nævnt har Dwarf rotter forhøjede niveauer af ghrelin, sult-hormonet, hvilket kan bidrage til fedme. Dette kan tilskrives det faktum, at Dwarf rotter har en lavere stofskifte sammenlignet med standard rotter. Som følge heraf kan fedtvæv (kropsfedt) ophobes i SDR-rotter på grund af betydeligt lavere energiforbrug i forhold til energiindtag. Interessant nok oplever SDR-rotter, på trods af at have mere kropsfedt end standard rotter, en stigning i visceralt fedt (fedt omkring de indre organer), når de bliver ældre, ligesom andre rotter. Disse to fedt typer er ikke den samme type fedt, og visceralt fedt er den farligste form, fordi det sidder omkring de indre organer i bughulen, herunder leveren, bugspytkirtlen og nyrerne. Den overskydende kropsfedt ser dog ikke ud til at påvirke deres levetid negativt. På trods af at være stort set fri for kræft og have en forlænget levetid, viser SDR-rotter et mindre fald i rumlig indlæring og hukommelse. I en Y-labyrint-test, hvor rotten placeres i en af de tre arme af labyrinten (hver arm måler 40 cm), er SDR-rotter mindre tilbøjelige til at ændre deres rute og udforske alle arme. Dette tyder på nedsat rumlig indlæring og hukommelse sammenlignet med standard rotter. De nøjagtige mekanismer bag stadig er uklare. Referencer:
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