Maternally and Paternally inherited Ddc, Gene Expression. Mus musculus strain:C57

Noncanonical genomic imprinting can cause biased expression of one parental allele in a tissue; however, the functional relevance of such biases is unknown. To investigate ethological roles for noncanonical imprinting in dopa decarboxylase (Ddc) and tyrosine hydroxylase (Th), we use machine learning to decompose naturalistic foraging in maternal and paternal allele mutant heterozygous mice.We uncover distinct roles for the maternal versus paternal alleles on foraging, where maternal alleles affect sons, while daughters are under paternal allelic control. Each parental allele controls specific action sequences reflecting decisions in naive or familiar contexts. The maternal Ddc allele is preferentially expressed in subsets of hypothalamic GABAergic neurons, while the paternal allele predominates in subsets of adrenal cells. Each Ddc allele affects distinct molecular and endocrine components of the Brain-Adrenal axis. Thus, monoaminergic noncanonical imprinting has ethological roles in foraging and endocrine functions, and operates by affecting discrete subsets of cells.

非经典基因组印记（noncanonical genomic imprinting）可导致某一亲本等位基因在组织中呈现偏倚表达，但此类偏倚表达的功能相关性仍不明确。为探究多巴脱羧酶（Ddc）与酪氨酸羟化酶（Th）相关的非经典基因组印记的行为学功能，我们借助机器学习对母源及父源等位基因突变杂合小鼠的自然觅食行为进行分解分析。我们发现亲本等位基因在觅食行为中发挥截然不同的作用：母源等位基因影响雄性子代，而雌性子代则受父源等位基因调控。每一类亲本等位基因均调控特定的动作序列，该序列对应个体在初次接触或熟悉环境下的决策行为。母源Ddc等位基因优先在下丘脑γ-氨基丁酸（GABA）能神经元亚群中表达，而父源等位基因则主要在肾上腺细胞亚群中富集。两类Ddc等位基因分别影响脑-肾上腺轴（Brain-Adrenal axis）中不同的分子与内分泌组分。综上，单胺能非经典基因组印记在觅食行为与内分泌功能中发挥行为学作用，其调控机制通过作用于特定的细胞亚群实现。