# Developing genetic access to group II proprioceptive muscle afferents

> **NIH NIH R03** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $164,500

## Abstract

SUMMARY
The proprioceptive sense largely derives from two specialized receptor organs in skeletal muscle: muscle
spindles (MSs) and Golgi tendon organs (GTOs). The afferents associated with these sensory end organs are
groups Ia and II MS-afferents and group Ib GTO afferents, which relay information about limb movement and
position (MS), or muscle load (GTO) from the peripheral receptors to the spinal cord and brainstem. MS afferents
are the primary kinesthetic sensors that enhance their firing rates with increases in muscle length, which in turn
serves as an indirect readout of joint position. While MS group Ia afferent can relay dynamic changes, MS group
II afferents are, on average, more sensitive for static stretch when compared to group Ia afferents and are far
more numerous. These observations have led to the idea that group II afferents are the main mediators of limb
and body position sense. Group II afferents therefore not only play a key role in various motor functions, but also
are central to the sense of self and agency, the sense of being in control of one’s actions. Despite their
importance, systematic analyses of group II function or their downstream neural circuits remains scarce.
 Historically, a key difficulty in studying group II afferents has been the inability to clearly distinguish them
from MS group Ia afferents through physiological or genetic means. Most stimuli that activate group II’s will also
activate group Ia’s and genetic reporters for individual proprioceptor subtypes were not yet identified. In recent
years, however, my lab identified expression of Neurexophilin 1 (Nxph1), a member of the Neurexophilin family
of secreted glycoproteins as a universal marker for MS group II afferents. Additional expression analyses indicate
that the Nxph1 locus offers a unique opportunity to study the development, circuitry and function of mouse group
II proprioceptive muscle afferents. Towards this goal, this proposal will develop and validate a novel Nxph1:Cre
animal model to enable the selective manipulation of adult group II muscle spindle afferents. These experiments
will provide the research community with a new genetic mouse model that will be essential for the study of group
II muscle afferents in health and disease.

## Key facts

- **NIH application ID:** 10951984
- **Project number:** 1R03NS139043-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Joriene De Nooij
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $164,500
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951984

## Citation

> US National Institutes of Health, RePORTER application 10951984, Developing genetic access to group II proprioceptive muscle afferents (1R03NS139043-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10951984. Licensed CC0.

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