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Analysis of Motor Function in Amyloid Precursor-Like Protein 2 Knockout Mice: The Effects of Ageing and Sex

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Abstract

The amyloid precursor protein (APP) is a member of a conserved gene family that includes the amyloid precursor-like proteins 1 (APLP1) and 2 (APLP2). APP and APLP2 share a high degree of similarity, and have overlapping patterns of spatial and temporal expression in the central and peripheral tissues, in particular at the neuromuscular junction. APP-family knockout (KO) studies have helped elucidate aspects of function and functional redundancy amongst the APP-family members. In the present study, we investigated motor performance of APLP2-KO mice and the effect sex differences and age-related changes have on motor performance. APLP2-KO and WT (on C57Bl6 background) littermates control mice from 8 (young adulthood) to 48 weeks (middle age) were investigated. Analysis of motor neuron and muscle morphology showed APLP2-KO females but not males, had less age-related motor function impairments. We observed age and sex differences in both motor neuron number and muscle fiber size distribution for APLP2-KO mice compared to WT (C57Bl6). These alterations in the motor neuron number and muscle fiber distribution pattern may explain why female APLP2-KO mice have far better motor function behaviour during ageing.

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Abbreviations

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

APLP1:

Amyloid precursor-like protein 1

APLP2:

Amyloid precursor-like protein 2

EDL:

Extensor digitorium longus

GA:

Gastrocnemius

OCT:

Optimal cutting temperature

PBS:

Phosphate buffered saline

PLA:

Plantaris

ROI:

Regions of interest

SOL:

Soleus

TA:

Tibialis anterior

WT:

Wildtype

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Acknowledgements

This study was supported by National Health and Medical Research Council of Australia to RC. PHT was a recipient of a Nancy Frances Curry PhD Scholarship. We thank the School of Biomedical Sciences animal facility staff for assisting with animal care and handling, and the School of Biomedical Sciences Histology Facility for its resources. We thank Paul Kennedy, Alfred Health, for their assistance with the ATPase staining protocol. We thank Prof Sangram Sisodia for the APLP2 knockout mice.

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  1. Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, VIC, 3010, Australia

    Phan H. Truong, Giuseppe D. Ciccotosto & Roberto Cappai

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  1. Phan H. Truong
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Correspondence to Roberto Cappai.

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Special issue: In honor of Prof. Anthony J. Turner.

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Truong, P.H., Ciccotosto, G.D. & Cappai, R. Analysis of Motor Function in Amyloid Precursor-Like Protein 2 Knockout Mice: The Effects of Ageing and Sex. Neurochem Res 44, 1356–1366 (2019). https://doi.org/10.1007/s11064-018-2669-6

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