Characterization of growth in a galactose-1-phosphate uridylyltransferase-null rat model of classic galactosemia Pubblico
Desai, Ronake (Spring 2021)
Abstract
A common long-term complication in treated children and adolescents with classic galactosemia (CG) is growth delay. Growth has been evaluated in multiple studies of human patients, and decreased height and weight is delayed in children and adolescents but normalized by adulthood. In the present study, we utilized our GALT-null rat model to test for growth differences between WT and GALT-null rats at multiple pre-pubertal time points. We assessed total body mass at discrete times and percent change in mass over multiple intervals of time. Using these metrics, we have characterized growth in our model and observed that total body mass in GALT-null rats is decreased compared to WT rats at discrete time points and that GALT-null rats experience a delayed pre-pubertal growth spurt.
Table of Contents
Chapter 1: Galactose and Classic Galactosemia .......................................................................... 1
Galactose and Its Metabolism.................................................................................................. 1
Classic Galactosemia (CG)....................................................................................................... 3
Normal Early Growth in Humans........................................................................................... 4
Growth Delay in Patients with CG.......................................................................................... 5
Chapter 2: Mammalian Models of GALT-Deficiency .................................................................. 8
The History of GALT Deficient Rodent Models .................................................................... 8
Previous Growth Findings in the SD-GALTM3 Model of GALT Deficiency..................... 10
Chapter 3: Methods for Quantifying Growth Differences in GALT-null Rats ......................... 13
Preparation of Litters ............................................................................................................. 13
Collection of Weight Data ...................................................................................................... 13
Rat Diet .................................................................................................................................... 13
Statistical Analysis 1: Male vs. Female Mass Comparisons of WT, Heterozygous, and GALT-null rats (Days 1-21) ................................................................................................... 14
Statistical Analysis 2: Mass Comparisons between WT and GALT-null Rats at 1, 8, 14, and 21 Days.............................................................................................................................. 14
Statistical Analysis 3: Weekly Percent Change in Mass (Days 1-7, 7-14, and 14-21) ....... 14
Statistical Analysis 4: Daily Percent Change in Mass (Days 15-31)................................... 15
Chapter 4: Results........................................................................................................................ 16
Male vs. Female Mass Comparisons of WT, Heterozygous, and GALT-null rats (Days 1, 14, and 21)................................................................................................................................ 16
Mass Comparisons between Single-Sex Cohorts of WT and GALT-null Rats at 1, 8, 14, and 21 Days.............................................................................................................................. 16
Weekly Percent Change in Total Body Mass (Days 1-7, 7-14, and 14-21) Among WT and GALT-null Rat Pups .............................................................................................................. 17
Daily Percent Change in Total Body Mass (Days 15-31) between WT and GALT-null Rat Pups .......................................................................................................................................... 17
Data Figures ............................................................................................................................ 19
Chapter 5: Discussion.................................................................................................................. 27
Sex is a significant predictor of mass in WT rats................................................................. 27
Total body mass is lower in single-sex GALT-null rat cohorts at ages 1-, 8-, 14-, and 21- days........................................................................................................................................... 27
Weekly percent change in mass reveals a pre-pubertal growth spurt in WT and GALT- null rats .................................................................................................................................... 27
Daily percent change in mass reveals time of peak pre-pubertal growth spurt is delayed in both male and female GALT-null rats ............................................................................. 28
Limitations and Future Directions ........................................................................................ 29
Appendix....................................................................................................................................... 30
Supplementary Tables and Figures....................................................................................... 30
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Characterization of growth in a galactose-1-phosphate uridylyltransferase-null rat model of classic galactosemia () | 2021-04-28 17:22:41 -0400 |
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